Toxic Soup: How the Chemistry of Cooking is Making You Sick

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15964246 - witch making toxic soup

dreamstime_40202494Raw food is what we ate for thousands of years before the invention of fire about 100,000 years ago. Once we discovered the amazing chemistry of cooking we have populated all the earth, even remote inhospitable areas where eating cooked food is necessary for survival. So everything we now know thousands of years later is actually part of a survival paradigm and has nothing to do with what is ultimately best under ideal circumstances, i.e., fresh, live raw food.

You see, all the rules for eating that we have in most cultures today are based on the “survival” paradigm which doesn’t actually apply to a real raw foodist. Things that may be a bit hard to digest when raw are actually not even necessary for a raw food lifestyle, such as cruciferous veggies. Digestive problems some people associate with eating raw food are actually caused by a digestive system that is “WEAKENED” by a lifetime of adaptation to cooked foods. Fortunately, it only takes a compromised digestive system a few months to adapt to a raw diet, and In a rare worst case scenario that may be years for people with serious digestive issues.

Some people consider nutrient absorption a problem with raw foods, since some cooked veggies only release nutrients after cooking. However, since raw food has much more nutrition and no toxins from cooking, you probably won’t need to eat those rare cooked exceptions at all on a raw food diet.

Of course, some foods may be a problem for a digestive system that is already compromised and adapted to cooked foods, but that’s not a problem caused by eating raw food. Over time, your body will get used to raw food and eventually those problems will just fall away. And, it is possible to retrain your digestive system to accept more raw foods without these problems.

The chemistry of cooking our food also results in the biggest nutritional and health problems of all — the numerous and insidious chemical changes to the food molecules caused by heat. This creates the carcinogens, mutagens and free radicals which ultimately are the real causes for most of the health problems in the world, even America, which cooked food eaters unfortunately assume are normal — but which are not. The enzymes in raw foods are mistakenly hyped a lot even by raw foodists, but enzymes are not the real big deal since our digestive system can makes those anyway. The big deal about raw food is the lack of any of the toxins commonly associated with the chemistry of cooking that cause most diseases!

The Chemistry of Cooking is like a High School Experiment.

The chemistry of cooking our food is like doing a chemistry experiment in high school. Due to heat, cooking or preparing food creates new substances. Most of these new substances come from proteins reacting with carbohydrates. Some of these substances cause cancer or brain diseases and impair neurotransmitter function and metabolism.

Many of these new substances are heterocyclic amines (HCA). Many of these HCA are directly or indirectly physically addictive.(1)   Due to the heat of cooking, these HCA originate from the interaction between protein and carbohydrates and / or creatine (in red meat) or nitrate (in vegetables). Some examples :

  • tryptophan + form- / acetaldehyde  = 1-methyl-1,2,3,4-tetrahydro-beta-carboline (pro-mutagenic) (2)
  • tryptophan + glycolaldehyde  = 1-hydroxymethyl-tetrahydro-beta-carboline (3)
  • tryptophan + sugars (by freezing)  = 1,1′-ethyliden-ditryptofaan (very toxic) (4)
  • serotonine + formaldehyde   = 6-hydroxy-tetrahydro-beta-carboline (5)
  • serotonine + acetaldehyde  = 6-hydroxy-1-methyl-tetrahydro-beta-carboline (6)
  • tyramine + nitrite  = 3-diazotyramine(4-(2-aminoethyl))-6-diazo-2,4-cyclohexadienone (carcin.)(7)
  • salt + nitrite + protein / sugar  = 2-chloro-4-methylthiobutanoate (mutagenic) (8)
  • glutamate + sugars  = 2-amino-6-methyldipyrido-(1,2-a:3′,2′-dimidazole (carcinogenic) (9)
  • glutamate + sugars  = 2-aminodipyrido-(1,2-a:3′,2′-dimidazole (carcinogenic)(9)

When aldehydes react upon cyclic amino acids or -amines (like tryptophan, tryptamine, serotonine, phenylalanine, tyrosine, dopamine, tyramine, aniline), mostly beta-carbolines and isoquinolines originate. When creatinine (from meat) is involved, mostly imidazoquinolines and imidaziquinoxalines originate. (10) (Glutamate and tryptophan are amino acids, tyramine and serotonine are amines, and aldehydes are sugars) .

In What Foods?

Almost all cooked or prepared foods contain:

  • 9H-pyrido(3,4-b)indole  = beta-carboline  = tryptophan / tryptamine + aldehydes (11)
  • 1-methyl-9H-pyrido(3,4-b)indole  = 1-methyl-beta-carboline  = tryptophan / tryptamine + aldehydes (11)

These substances influence benzodiazepine receptors in the brain, and indirectly lots of other neurotransmitters. (12) If these substances further react upon amines like aniline, they even become mutagenic (23). How much HCA originate depends on how much protein the food contains and on how much the food is heated. (14)   Because red meat contains both lots of protein and creatinine (creating creatine), prepared red meat contains the most HCA, especially when grilled (15). Besides prepared red meat, also prepared fish, soy and poultry contain lots of HCA. (16) Flavor-enhancers and bouillon contain protein-concentrates and therefore contain lots of HCA too. (11) But also prepared foods containing less protein contain HCA, like prepared grains (17) and -vegetables (18), and even foods like beer, soy sauce and canned orange juice. (19) For example:

Meat contains too much creatine (20):

  • 2-amino-1-methyl-6-(4-hydroxyfenyl)-imidazo-(4,5-b)pyridine (mutag.)  = creatine + tyrosine + glucose (21)

Soy contains globulins:

  • 2-amino-9H-pyrido(2,3-b)indole  (mutagenic) (22)  = soy-globulins + sugars (23)
  • 2-amino-3-methyl-9H-pyrido(2,3-b)indole (mutagenic) (24)  = soy-globulins + sugars (23)

Prepared fish contains (25):

  • 3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole (mutagenic)(26)  = tryptophan + acetaldehyde (27)
  • 3-amino-1-methyl-5H-pyrido(4,3-b)indole (mutagenic)(26) = tryptophane + acetaldehyde (28)

Cooked Vegetables contain nitrite:

  • cancerous N-nitroso-compounds = amines + nitrite + sugars
  • specific N-nitroso-compound ;
  • 4-(2-aminoethyl)-6-diazo-2,4-cyclohexadienone (cancerous) = tyramine + nitrite + sugars (7)

Cooked Cabbages contain thiocyanates ;

  • toxic (29) tetrahydro-beta-carboline-derivates = isothiocyanate + tyramine / serotonine etc.

Cooked vegetables contain also flavonoids:

  • mutagenic glycosides (30)  = flavonods + heat

Canned orange juice contains free amino acids, which easily combine with aldehydes to create heterocyclic amines.

What Can HCA Do?

1. Act like Neurotransmitters

Some HCA, like beta-carbolines, can directly influence neurotransmitter-receptors, like benzodiazepine receptors. Simply because the body also composes beta-carbolines to function as neurotransmitters. HCA can also occupy receptors of other neurotransmitters, like serotonine- and dopamine receptors. Especially when they are composed of the same amines. Some examples ;

  • 3-methoxycarbonyl-beta-carboline acts through different receptors (31) and increases secretion and decomposition of dopamine, like physical stress does. (32) It enhances ‘irrational’ aggressive behaviour (33), and decreases social interaction (34).
  • 3-ethoxycarbonyl-beta-carboline, is hypnotic and anaesthetic (35), and inhibits investigative behaviour (36) and social interaction. (37) In dominant types it enhances aggressive behaviour, but inhibits sexual appetite. (38) It increases epinephrine-   (39) and cortisol-level, blood pressure and heart rate (40), and increases secretion and decomposition of dopamine (41), like physical stress does.
  • 3-Hydroxymethyl-beta-carboline ; though hypnotic (42), it negatively affects sleep (43).
  • 3-N-methylcarboxamide-beta-carboline enhances reckless- (44) and aggressive behaviour (45), and inhibits sexual appetite. (46) It generally inhibits (47), but locally stimulates norepinephrine secretion. (48) It increases glutamate- (49), ACTH- and Substance P-secretion (50), increases blood pressure (51) and though anaesthetic (52), causes physical stress. (53).
  • 3-Methylcarbonyl-6,7-dimethoxy-4-ethyl-beta-carboline blocks GABA receptors (54), increases GABA- and glycine-level, decreases glutamate- and aspartate-level (55), increases corticosterone-, epinephrine- and norepinephrine-secretion(56), decreases serotonine-secretion (57) and increases norepinephrine-receptor-activity. (58) It enhances the effect of cocaine (59), causes anxiety (60) and suppresses immune system activity. (61)
  • 3-Ethylcarbonyl-6-benzyloxy-4-methoxymethyl-beta-carboline is sedative (62), causes amnesia (63), and blocks beta-oestradiol-LH (lutinizing hormone) interaction. (64)
  • 3-Ethylcarbonyl-5-benzyloxy-4-methoxymethyl-beta-carboline strongly stimulates appetite. (65)
  • 3-Ethylcarbonyl-5-isopropyl-4-methyl-beta-carboline causes restlessness (66), sleeplessness (67), and decreases social interaction. (68)

Besides ‘normal’ beta-carbolines, prepared foods also contain tetrahydro-beta-carbolines. (69).

  • Tetrahydro-beta-carboline stimulates craving for alcohol (70), increases heart rate and blood pressure (71), and like 5-methoxy-tetrahydro-beta-carboline and 5-hydroxy-tetrahydro-beta-carboline increases prolactine-level and affects serotonine receptors. (72)
  • 6-methoxy-tetrahydro-beta-carboline increases norepinephrine- and ACTH- secretion, and decreases serotonine- and growth hormone secretion. (73)
  • 2-Fenylpyrazolo(4,3-c)quinoline-3(5H)-one is sedative (74), increases corticosterone-level (75) and decreases specific benzodiazepine-receptors in the brain. (76)

2. Cause Cancer

Part of the process causing cancer is mutagenic substances damaging cell-DNA. (see site5) Some HCA in prepared food are mutagenic.DNA-damage increases linearly with intake of HCA. (77) How cancerous HCA are is partly dependent on how much nitrogen they contain. (78) Salt, protein and nitrite (from vegetables) can supply nitrogen to react upon HCA. And nitrosated HCA are even more cancerous. (79) Some of the most widespread mutagenic HCA in prepared foods are:

  • pyridoindole (80) (amino-gamma-carboline)
  • 2-amino-9H-pyrido(2,3-b)indole(81) (amino-alpha-carboline)
  • 2-amino-3-methyl-9H-pyrido(2,3-b) (82)
  • 3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole(83)
  • 3-amino-1-methyl-5H-pyrido(4,3-b)indole(84)
  • 1-methyl-3-carbonyl-1,2,3,4-tetrahydro-beta-carboline(85).
  • 4-aminobiphenyl(86)
  • 4,4′-methylenedianiline (87)
  • 3,2′-dimethyl-4-aminobiphenyl(88)
  • 1,2-dimethylhydrazine(89)
  • phenyl-hydroxylamine (90)
  • O-acetyl-N-(5-phenyl-2-pyridyl)-hydroxylamine(91)
  • 2-amino-3-methylimidazo(4,5-f)quinoline(92)
  • 2-amino-3-methylimidazo(4,5-f)quinoxaline(93)
  • 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (94)
  • 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (95)
  • 2-amino-3,4,8-trimethylimidazo(4,5-b)pyridine(96)
  • 2-amino-3,4,8-trimethylimidazo(4,5-f)quinoxaline (97)
  • 2-amino-3,7,8-trimethylimidazo(4,5-f)-quinoxaline(98)
  • 2-amino-n,n,n-trimethylimidazo-pyridine(99)
  • 2-amino-n,n-dimethylimidazopyridine (100)
  • 2-amino-4-hydroxymethyl-3,8-dimethylimidazo-(4,5-g)-quinoxaline(101)
  • 2-amino-1,7,9-trimethylimidazo-(4,5-g)-quinoxaline (101)
  • 2-amino-1-methyl-6-phenylimidazo-(4,5-b)-pyridine(102)

3. Cause Brain Diseases

Some HCA are directly toxic to the brain, like common quinolines, which enter the brain through the dopamine-transport system. (103)  Other common HCA (like pyridines (104) and beta-carbolines (105)) only become toxic to the brain after they have been partly decomposed by different enzymes (106) in the body. Originally , these enzymes have to, and do protect the brain against toxic substances, but part of the HCA are accidentally transformed into more toxic substances. (107) Obviously nature didn’t count on ‘strange’ HCA from prepared food. Pyridines can only occupy dopamine-receptors (108), and therefore are toxic to thesereceptors only. Partly decomposed pyridines are more toxic than the originals (109), but the originals do decrease dopamine- (110), norepinephrine- (111) and mostly serotonine-level (112). The destruction of receptors in the brain causes brain-diseases like Alzheimer’s, Parkinson’s and schizophrenia. Some toxic-to-the brain HCA are:

  • 3-N-butylcarbonyl-beta-carboline (113)
  • 3-N-methylcarboxamide-beta-carboline(113)
  • 2-methyl-1,2,3,4-tetrahydro-beta-carboline(114)
  • 2-methyl-1,2,3,4-tetrahydro-isoquinoline(114)
  • quinolinate (115)
  • quisqualinate (116)
  • tetrahydroisoquinoline(117)
  • 1-benzyl-tetrahydro-isoquinoline(117)
  • N-methyl-(R)-salsolinol(118)
  • N-methyl-6-methoxy-1,2,3,4-tetrahydro-isoquinoline(119)
  • 6-methoxy-1,2,3,4-tetrahydro-isoquinoline(119)
  • 2,4,5-trihydroxyphenylalanine(120)
  • 6-hydroxy-dopamine(121)
  • N-methyl-4-fenyl-1,2,3,6-tetrahydropyridine(122)
  • 1-methyl-4-fenyl-1,2,3,6-tetrahydropyridine(123)
  • 1-methyl-4-fenyl-1,2,5,6-tetrahydropyridine(124).
  • 4-fenyl-1,2,3,6-tetrahydropyridine(125)
  • 4-fenylpyridine(125)
  • 3-acetylpyridine(126)
  • 1-methyl-4-phenyl-1,4-dihydropyridine(127)
  • 1-methyl-4-cyclohexic-1,2,3,6-tetrahydropyridine(128)
  • 1-methyl-4-(2′-methylfenyl)-1,2,3,6–tetrahydropyridine (129)
  • 1-methyl-4-(2′-ethylfenyl)-1,2,3,6-tetrahydropyridine (130)
  • 1-methyl-4-(3′-methoxyfenyl)-1,2,3,6-tetrahydropyridine(131)
  • 1-methyl-4-(methylpyrrol-2-yl)-1,2,3,6-tetrahydropyridine(132)

Though toxic pyridines create oxidative radicals (133) and decrease antioxidant-level (134), the intake of antioxidants cannot prevent brain damage by toxic pyridines. (135)

Additives

Food preparation exists primarily to make things edible that really are not so edible. Additives are primarily there to make fake food last longer, and to make you eat more. Taste enhancers for example are mostly concentrated protein, filled with lots of physically-addictive beta-carbolines that make you eat more. Glutamate (popular in the Chinese kitchen) indirectly influences the same (Benzodiazepine) receptors.

Adapted from ”New Substances In Prepared Food” by Wai Genriiu.
Copyright 2001 by Wai Genriiu, Adapted 2006-2017 by Robert Ross, RawFoodLife, LLC. Abstracts of most sources can be found at  the National Library of Medicine.

  • Loscher, W. et al, Withdrawal precipation by benzodiazepine receptor antagonists in dogs chronically treated with diazepam or the novel anxiolytic and anticonvulsant beta-carboline abecarnil. Naunyn Schmiedebergs Arch. Pharmacol. 1992 / 345 (4) / 452-460.
  • De Boer, S.F. et al, Common mechanisms underlying the proconflict effects of corticotropin, a benzodiazepine inverse agonist and electric foot shock. J. Pharmacol. Exp. Ther. 1992 / 262 (1) / 335-342.
  • Little, H.J. et al, The benzodiazepines : anxiolytic and withdrawal effects. Neuropeptides 1991 / 19 / suppl. 11-14.
  • Eisenberg, R.M. et al, Effects of beta-carboline-ethyl ester on plasma corticosterone -- a parallel with antagonist-precipated diazepam withdrawal. Life Sci. 1989 / 44 (20) / 1457-1466.
  • (no author listed) Tetrahydro-beta-carbolines in foodstuffs, urine, and milk : physiological implications. Nutr. Rev. 1991 / 49 (12) / 367-368.
  • Papavergou, E. et al, Tetrahydro-beta-carboline-carboxylic acids in smoked foods. Food Addit. Contam. 1992 / 9 (1) / 83-95.
  • Rommelspacher, H. et al, Is there a correlation between the concentration of beta-carbolines and their pharmacolodynamic effects ? Prog. Clin. Biol. Res. 1982 / 90 / 41-55.
  • Wakabayashi, K. et al, Recently identified nitrite-reactive compounds in food : occurrence and biological properties of the nitrosated products. IARC Sci. Publ. 1987 / 84 / 287-291.
  • (8) Jolivette, L.J. et al, Thietanium ion formation from the food mutagen 2-chloro-4-(methylthio)butanoic acid. Chem. Res. Toxicol. 1998 / 11 (7) / 794-799.
  • Sugimura, T. et al, Carcinogenic, Mutagenic, and Comutagenic Aromatic Amines in Human Foods. Natl. Cancer Inst. Monogr. 1981 / 58 / 27-33.
  • Overvik, E. et al, Influence of creatine, amino acids and water on the formation of the mutagenic heterocyclic amines found in cooked meat. Carcinogenesis 1989 / 10 (12) / 1293-1301. , Yoshida, D. et al, Formation of mutagens by heating foods and model systems. Environ. Health. Perspect. 1986 / 67 / 55-58.
  • Solyakov, A. et al, Heterocyclic amines in process flavours, process flavour ingredients, bouillon concentrates and a pan residue. Food Chem. Toxicol. 1999 / 37 (1) / 1-11.
  • Skog, K. et al, Analysis of nonpolar heterocyclic amines in cooked foods and meat extracts using gas chromatography-mass spectometry. J. Chromatogr. A. 1998 / 803 (1-2) / 227-233.
  • Stavric, B. et al, Mutagenic heterocyclic aromatic amines (HAA's) in 'processed food flavour' samples. Food Chem. Toxicol. 1997 / 35 (2) / 185-197.
  • Wakabayashi, K. et al, Human exposure to mutagenic / carcinogenic heterocyclic amines and comutagenic beta-carbolines. Mutat. Res. 1997 / 376 (1-2) / 253-259.
  • Galceran, M.T. et al, Determination of heterocyclic amines by pneumatically assisted electrospray liquid chromatography-mass spectometry. J. Chromatogr. A. 1996 / 730 (1-2) / 185-194.
  • Gross, G.A. et al, Heterocyclic aromatic amine formation in grilled bacon, beef and fish and in grilled scrapings. Carcinogenesis 1993 / 14 (11) / 2313-2318.
  • Sugimura, T. et al, Mutagenic factors in cooked foods. Crit. Rev. Toxicol. 1979 / 6 (3) / 189-209.
  • Rommelspacher, H. et al, beta-Carbolines and tetrahydroisoquinolines : detection and function in mammals. Planta. Med. 1991 / 57 (7) / 585-592. ,
  • Pawlik, M. et al, Quantitative autoradiograph of (3H)norharman ((3H)beta-carboline) binding sites in the rat brain. J. Chem. Neuroanal. 1990 / 3 (1) / 19-24. , Rommelspacher, H. et al, Harman induces preference for ethanol in rats : is the effect specific for ethanol ? Parhmacol. Biochem. Behav. 1987 / 26 (4) / 749-755. ,
  • Rommelspacher, H. et al, Benzodiazepine antagonism by harmane and other beta-carbolines in vitro and in vivo. Eur. J. Pharmacol. 1981 / 70 (3) / 409-416.
  • Totsuka, Y. et al, Structural determination of a mutagenic aminophenylnorharman produced by the co-mutagen norharman with aniline. Carcinogenesis 1998 / 19 (11) / 1995-2000. , Skog, K. et al, Analysis of nonpolar heterocyclic amines in cooked foods and meat extracts using gas chromatography-mass spectometry. J. Chromatogr. A. 1998 / 803 (1-2) / 227-233.
  • Vikse, R. et al, Heterocyclic amines in cooked meat. (in Norwegian) Tidsskr. Nor. Laegeforen. 1999 / 119 (1) / 45-49. , Sinha, R. et al, Heterocyclic amine content of pork products cooked by different methods and to varying degrees of doneness. Food Chem. Toxicol. 1998 / 36 (4) / 289-297. ,
  • Byrne ,C. et al, Predictors of heterocyclic amines intake in three prospective cohorts. Cancer Epidemiol. Biomarkers 1998 / 7 (6) / 523-529. , Kaplan, S. et al, Nutritional factors in the etiology of brain tumors : potential role of nitrosamines, fat, and cholesterol. Am. J. Epidemiol. 1997 / 146 (10) / 832-841. ,
    Ward, M.H. et al, Risk of adenocarcinoma of the stomach and esophagus with meat cooking method and doneness preference. Int. J. Cancer 1997 / 71 (1) / 14-19. ,
  • La Vecchia, C. et al, Selected micronutrient intake and the risk of gastric cancer. Cancer Epidemiol. Biomarkers Prev. 1994 / 3 (5) / 393-398. ,
  • Buiatti, E. et al, A case-control study of gastric cancer and diet in Italy : II. Association with nutrients. Int. J. Cancer 1990 / 45 (5) / 896-901. , Proliac, A. et al, Isolation and identification of two beta-carbolins in roasted chicory root. Helv. Chim. Acta 1976 / 59 (7) / 2503-2507. (in french)
  • Salmon, C.P. et al, Effects of marinating on heterocyclic amine carcinogen formation in grilled chicken. Food Chem. Toxicol. 1997 / 35 (5) / 433-441. , Shibata, A. et al, Dietary beta-carotene, sigarette smoking and lung cancer in men. Cancer Causes Control 1992 / 3 (3) / 207-214.
  • Chiu, C.P. et al, Formation of heterocyclic amines in cooked chicken legs. J. Food Prot. 1998 / 61 (6) / 712-719. , Byrne, C. et al, Predictors of dietary heterocyclic amine intake in three prospective cohorts. Cancer Epidemiol. Biomarkers Prev. 1998 / 7 (6) / 523-529. ,
  • Wakabayashi, K. et al, Human exposure to mutagenic / carcinogenic heterocyclic amines and co-mutagenic beta-carbolines. Mutat. Res. 1997 / 376 (1-2) / 253-259. ,
  • Salmon, C.P. et al, Effects of marinating on heterocyclic amine carcinogen formation in grilled chicken. Food Chem Toxicol. 1997 / 35 (5) / 433-441. ,
  • Skog, K. et al, Polar and non-polar heterocyclic amines in cooked fish and meat products and their corresponding pan residues. Food Chem. Toxicol. 1997 / 35 (6) / 555-565. ,
  • Pfau, W. et al, Characterization of the major DNA adduct formed by the food mutagen 2-amino-3-methyl-9H-pyrido(2,3-b)indole (MeAalphaC) in primary rat hepatocytes. Carcinogenesis 1996 / 17 (12) / 2727-2732. ,
  • Thiebaud, H.P. et al, Airborne mutagens produced by frying beef, pork and soy-based food. Food and Chemical Toxicology 1995 / 10 / 821-828. , Ohgaki, H. et al, Carcinogenicity in mice of mutagenic compounds from glutamic acid and soybean globulin pyrolysates. Carcinogenesis. 1984 / 5 (6) / 815-819. ,
  • Tomita, I. et al, Mutagenicity of various Japanese foodstuffs treated with nitrite. II. Directly acting mutagens produced from N-containing compounds in foodstuffs. IARC Sci. Publ. 1984 / 57 / 33-41.
  • Knize, M.G. et al, Characterization of mutagenic activity in cooked-grain-food products. Food Chem. Toxicol. 1994 / 32 (1) / 15-21.
  • Ozawa, Y. et al, Occurence of stereoisomers of 1-(2'-pyrrolidinethione-3'-yl)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid in fermented radish roots and their different mutagenic properties. Biosci. Biotechnol. Biochem. 1999 / 63 (1) / 216-219. ,
  • Sen, N.P. et al, Analytical methods for the determination and mass spectometric confirmation of 1-methyl-2-nitroso-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid and 2-nitroso-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid in foods. Food. Addit. Contam. 1991 / 8 (3) / 275-289. ,
  • Sugimura, T. et al, Mutagenic factors in cooked foods. Crit. Rev. Toxicol. 1979 / 6 (3) / 189-209.
  • Herraiz, T. et al, Presence of tetrahydro-beta-carboline-3-carboxylic acids in foods by gas chromatography-mass spectometry as their N-methoxycarbonylmethyl ester derivates. J. Chromatogr. A. 1997 / 765 (2) / 265-277.
  • Skog, K.I. et al, Carcinogenic heterocyclic amines in model systems and cooked foods : a revieuw on formation, occurence and intake. Food Chem. Toxicol. 1998 / 36 (9-10) / 879-896.
  • Kurosaka, R. et al, Detection of 2-amino-1-methyl-6-(4-hydroxyphenyl)imidazo(4,5-b) pyridine (4'-OH-PhIP) level comparable to PhIP. Jpn. J. Cancer Res. 1992 / 83 (9) / 919-922.
  • Okogoni, H. et al, Induction of aberrent cryptfoci in C57BL/6N mice by 2-amino-9H-pyrido(2,3-b)indole (AalphaC) and 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx) Cancer Lett. 1997 / 111 (1-2) / 105-109. ,
  • Zhang, X.B. et al, Intestinal mutagenicity of two carcinogenic food mutagens in transgenic mice : 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine and amino(alpha)carboline. Carcinogenesis 1996 / 17 (10) / 2259-2265. ,
  • Yoo, M.A. et al, Mutagenic potency of heterocyclic amines in the Drosophila wing spot test and its correlation to carcinogenic potency. Jpn. J. Cancer Res. 1985 / 76 (6) / 468-473.
  • Beamand, J.A. et al, Effect of some cooked food mutagens on unscheduled DNA synthesis in cultured precision-cut rat, mouse and human liver slices. Food Chem. Toxicol. 1998 / 36 (6) / 455-466. ,
  • Yoshida, D. et al, Formation of mutagens by heating foods and model systems. Environ. Health Perspect. 1986 / 67 / 55-58. ,
  • Ohgaki, H. et al, Carcinogenicity in mice of mutagenic compounds from glutamic acid and soybean globulin pyrolysates. Carcinogenesis. 1984 / 5 (6) / 815-819.
  • Pfau, W. et al, Characterization of the major DNA adduct formed by the food mutagen 2-amino-3-methyl-9H-pyrido(2,3-b)indole (MeAalphaC) in primary rat hepatocytes. Carcinogenesis 1996 / 17 (12) / 2727-2732. , Pfau, W. et al, Pancreatic DNA adducts formed in vitro and in vivo by the food mutagens 2-amino-1-methyl-6-phenylimidazo(4,5-b)prydine (PhIP) and 2-amino-3-methyl-9H-pyrido(2,3-b)indole (MeAalphaC). Mutat. Res. 1997 / 378 (1-2) / 13-22.
  • Skog, K. et al, Analysis of nonpolar heterocyclic amines in cooked foods and meat extracts using gas chromatography-mass spectometry. J. Chromatogr. A. 1998 / 803 (1-2) / 227-233.
  • Galceran, M.T. et al, Determination of heterocyclic amines by pneumatically assisted electrospray liquid chromatography-mass spectometry. J. Chromatogr. A. 1996 / 730 (1-2) / 185-194. Yamaguchi, K. et al, Presence of 3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole in broiled beef. Gann. 1980 / 71 (5) / 745-746. , Yamaizumi, Z. et al, Detection of potent mutagens, Trp-P-1 and Trp-P-2 in broiled fish. Cancer Lett. 1980 / 9 (2) / 75-83. Sugimura, T. et al, Mutagenic factors in cooked foods. Crit. Rev. Toxicol. 1979 / 6 (3) / 189-209.
  • shida, H. et al, Tryptophan pyrolysis products, Trp-P-1 and Trp-P-2 induce apoptosis in primary cultured rat hepatocytes. Biosci. Biotechnol. Biochem. 1998 / 62 (11) / 2283-2287.
  • Sasaki, Y.F. et al, In vivo genotoxicity of heterocyclic amines detected by a modified alkaline single cell gel electrophoresis assay in a multiple organ study in the mouse. Mutat. Res. 1997 / 395 (1) / 57-73.
  • Sugimura,T. et al, Mutagens in food. Journal of Agriculture and Food Chemistry 1995 / 43 / 404-414.
  • Manabe, S. et al, Carcinogenic tryptophan pyrolysis products in the environment. J. Toxicol. Sci. 1991 / 16 (suoppl.1) / 63-72.
  • Skog, K. et al, Analysis of nonpolar heterocyclic amines in cooked foods and meat extracts using gas chromatography-mass spectometry. J. Chromatogr. A. 1998 / 803 (1-2) / 227-233.
  • Galceran, M.T. et al, Determination of heterocyclic amines by pneumatically assisted electrospray liquid chromatography-mass spectometry. J. Chromatogr. A. 1996 / 730 (1-2) / 185-194.
  • Yamaguchi, K. et al, Presence of 3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole in broiled beef. Gann. 1980 / 71 (5) / 745-746.
  • Yamaizumi, Z. et al, Detection of potent mutagens, Trp-P-1 and Trp-P-2 in broiled fish. Cancer Lett. 1980 / 9 (2) / 75-83.
  • Sugimura, T. et al, Mutagenic factors in cooked foods. Crit. Rev. Toxicol. 1979 / 6 (3) / 189-209.
  • Ozawa, Y. et al, Occurence of stereoisomers of 1-(2'-pyrrolidinethione-3'-yl)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid in fermented radish roots and their different mutagenic properties. Biosci. Biotechnol. Biochem. 1999 / 63 (1) / 216-219.
  • Lopez-Rodrigeuz, M. et al, Reaction of 6-hydroxy-tetrahydro-beta-carboline-3-carboxylic acids with isocyanates and isothiocyanates. Chem. Pharm. Bull. Tokyo 1994 / 42 (12) / 2108-2112.
  • Sugimura, T. et al, Mutagenic factors in cooked foods. Crit. Rev. Toxicol. 1979 / 6 (3) / 189-209.
  • Burkard, W.P. et al, The benzodiazepine antagonist Ro15-1788 reverses the effect of methyl-beta-carboline-3-carboxylate, but not of harmiline on cerebellar cGMP and motorperformance in mice. Eur. J. Pharmacol. 1985 / 109 (2) / 241-247.
  • Serrano, A. et al, NMDA antagonists block restraint-induced increase in extracellular DOPAC in rat nucleus accumbens. Eur. J. Pharmacol. 1989 / 162 (1) / 157-166.
  • Claustre, Y. et al, Pharmacological studies on stress-induced increase in frontal cortical dopamine metabolism in the rat. J. Pharmacol. Exp. Ther. 1986 / 238 (2) / 693-700.
  • Holley, L.A. et al, Dissociation between the attentional effects of infusions of a benzodiazepine receptor agonist and inverse agonist into the basal forebrain. Psychopharmacology (Berl.) 1995 / 120 (1) / 99-108.
  • Shibata, S. et al, Effects of benzodiazepine and GABA antagonists on anticonflict effects of antianxiety drugs injected into the rat amygdala in a water-lick suppression test. Psychopharmacology 1989 / 98 (1) / 38-44.
  • Jones, B.J. et al, Microinjections of methyl-beta-carboline-3-carboxylate into the dorsal raphe nucleus : behavioral consequences. Pharmacol. Biochem. Behav. 1986 / 24 (5) / 1487-1489.
  • Tokuyama, S. et al, Blockade of the development of analgesic tolerance to morphine by psychological stress through benzodiazepine receptor mediated mechanism. Jpn. J. Pharmacol. 1989 / 51 (3) / 425-427.
  • Kaijima, M. et al, Hypnotic action of ethyl-beta-carboline-3-carboxylate, a benzodiazepine receptor antagonist, in cats. Electroencephalogr. Clin. Neurophysiol. 1984 / 58 (3) / 277-281.
  • Merlo Pick ,E. et al, A two compartment exploratory model to study anxiolytic / anxiogenic effects of drugs in the rat. Pharmacol. Res. 1989 / 21 (5) / 595-602.
  • Chermat, R. et al, Interactions of Ginkgo biloba extract (EGb 761), diazepam and ethyl-beta-carboline-3-carboxylate on social behaviour of the rat. Pharmacol. Biochem. Behav. 1997 / 56 (2) / 333-339.
  • Maestripieri, D. et al, Anxiety in rhesus monkey infants in relation to interactions with their mother and other social companions. Dev. Psychobiol. 1991 / 24 (8) / 571-581.
  • Hindley, S.W. et al, The effects of methyl-beta-carboline-3-carboxylate on social interaction microinjected into the nucleus raphe dorsalis of the rat. Br. J. Pharmacol. 1985 / 86 (3) / 753-761.
  • Vellucci, S.V. et al, The effect of midazolam and beta-carboline-3-carboxylate methyl ester on behaviour, steroid hormones and central monoamine metabolites in social groups of talapoin monkeys. Psychopharmacology (Berl.) 86 / 90 (3) / 367-372.
  • Skolnick, P. et al, A novel chemically induced animal model of human anxiety. Psychopathology 1984 / 17 (suppl.1) / 25-26.
  • Insel, T.R. et al, Rearing paradigm in a nonhuman primate affects response to beta-CCE challenge. Psychopharmacology (Berl.) 1988 / 96 (1) / 81-86.
  • Insel, T.R. et al, A benzodiazepine receptor-mediated model of anxiety studies in nonhuman primates and clinical implications. Arch. Gen. Psychiatry 1984 / 41 (8) / 741-750.
  • Ninan, P.T. et al, Benzodiazepine-mediated experimental ''anxiety'' in primates. Science 1982 / 218 (4579) / 1332-1334.
  • Murai, T. et al, Opposite effects of midazolam and beta-carboline-3-carboxylic acid-ethyl ester on the release of dopamine from rat nucleus accumbens measured by in vivo microdialysis. Eur. J. Pharmacol. 1994 / 261 (1-2) / 65-71.
  • Kalin, N.H. et al, Effects of beta-carbolines on fear-related behavioral and neurohormonal responses in infant rhesus monkeys. Biol. Psychiatry. 1992 / 31 (10) / 1008-1019.
  • Naughton, N. et al, A benzodiazepine antagonist inhibits the cerebral metabolic and respiratory depressant effects of fentanyl. Life Sci. 1985 / 36 (23) / 2239-2245.
  • Hoffman, W.E. et al, Cerebrovascular and cerebral metabolic effects of flurazepam and a benzodiazepine antagonist, 3-hydroxymethyl-beta-carboline. Eur. J. Pharmacol. 1984 / 106 (3) / 585-591.
  • Mendelson, W.B. et al, A benzodiazepine receptor antagonist decreases sleep and reverses the hypnotic actions of flurazepam. Science 1983 / 219 (4583) / 414-416.
  • Ongini, E. et al, Intrinsic and antagonistic effect of beta-carboline FG7142 on behavioral and EEG actions of benzodiazepines and pentobarbital in cats. Eur. J. Pharmacol. 1983 / 95 (1-2) / 125-129.
  • Adamec, R., Modelling anxiety disorder following chemical exposures. Toxicol. Ind. Health. 1994 / 10 (4-5) / 391-420.
  • Corda, M.G. et al, Long-lasting proconflict effects induced by chronic administration of the beta-carboline derivate FG7142. Neurosci. Lett. 1985 / 62 (2) / 237-240.
  • Agmo, A. et al, Benzodiazepine receptor ligands and sexual behavior in the male rat : the role of GABAergic mechanisms. Pharmacol. Biochem. Behav. 1991 / 38 (4) / 781-788.
  • Fung, S.C. et al, Multiple effects of drugs acting on benzodiazepine receptors. Neurosci. Lett. 1984 / 50 (1-3) / 203-207.
  • Nakane, H. et al, Stress-induced norepinephrine release in the rat prefrontal cortex measured by microdialysis. Am. J. Physiol. 1994 / 267 (6 Pt 2) / R1559-1566.
  • Ida, Y. et al, Anxiogenic beta-carboline FG7142 produces activity of neuroadrenergic neurons in specific brain regions of rats. Pharmacol. Biochem. Behav. 1991 / 39 (3) / 791-793.
  • Karreman, M. et al, Effect of a pharmacological stressor on glutamate efflux in the prefrontal cortex. Brain. Res. 1996 / 716 (1-2) / 180-182.
  • Donnerer, J. ,Evidence for an excitatory action of the benzodiazepine receptor inverse agonist FG7142 on C-fibre afferents. Naunyn Schmiedebergs Arch. Pharmacol. 1989 / 340 (3) / 352-354.
  • Webb, J.K. et al, Inhibition of pentgastrin-induced pressor response in conscious rats by the CCK-8 receptor antagonist Cl-988 and chlordiazepoxide. Regul. Pept. 1996 / 61 (1) / 71-76.
  • Rodgers, R.J. et al, Benzodiazepine ligands, noiception and 'defeat' analgesia in male mice. Psychopharmacology (Berl.) 1987 / 91 (3) / 305-315.
  • Soltis, R.P. et al, Cardiovascular effects of the beta-carboline FG7142 in borderline hypertensive rats. Physiol. Behav. 1998 / 63 (3) / 407-412.
  • Horger, B.A. et al, Selective increase in dopamine utilization in the shell subdivision of the nucleus accumbens by the benzodiazepine inverse agonist FG7142. J. Neurochem. 1995 / 65 (2) / 770-774.
  • Bradberry, C.W. et al, The anxiogenic beta-carboline FG7142 selectively increases dopamine release in rat prefrontal cortex as measured by microdialysis. J. Neurochem. 1991 / 56 (2) / 748-752.
  • Knorr, A.M. et al, The anxiogenic beta-carboline FG7142 increases in vivo and in vitro tyrosine hydroxylation in the prefrontal cortex. Brain. Res. 1989 / 495 (2) / 355-361.
  • Stanford, S.C. et al, A single dose of FG7142 causes long-term increase in mouse cortical adrenoceptors. Eur. J. Pharmacol. 1987 / 134 (3) / 313-319.
  • Ida, Y. et al, The activation of mesoprefrontal dopamine neurons by FG7142 is absent in rats treated chronically with diazepam. Eur. J. Pharmacol. 1987 / 137 (2-3) / 185-190.
  • Brose, N. et al, Effects of an anxiogenic benzodiazepine receptor ligand on motor activity and dopamine release in nucleus accumbens and stratium in the rat. J. Neurosci. 1987 / 7 (9) / 2917-2926.
  • Tietz, E.I. et al, Functional GABAA receptor heterogeneity of acutely dissociated hippocampal CA1 pyramidal cells. J. Neurophysiol. 1999 / 81 (4) / 1575-1586.
  • Vicini, S. et al, Actions of benzodiazepine and beta-carbolin derivates on gamma-amino-butyric acid-activated Cl-channels recorded from membrane patches of neonatal rat cortical neurons in culture. J. Pharmacol. Exp. Ther. 1987 / 243 (3) / 1195-1201.
  • Jensen, M.S. et al, Electrophysiological studies in cultured mouse CNS neurones of the actions of an agonist and inverse agonist at the benzodiazepine receptor. Br. J. Pharmacol. 1986 / 88 (4) / 717-731.
  • Chapman, A.G. et al, Effects of two convulsant beta-carboline derivates, DMCM and beta-CCM, on regional neurotransmitter amino acid levels and on in vitro D-(3H)-aspartate release in rodents. J. Neurochem. 1985 / 45 (2) / 370-381.
  • De Boer, S.F. et al, Effects of chlordiazepoxide, flumazenil and DMCM on plasma catecholamine and corticosterone concentrations in rats. Pharmacol. Biochem. Behav. 1991 / 38 (1) / 13-19.
  • Lista, A. et al, The benzodiazepine inverse agonist DMCM decreases serotonergic transmission in rat hippocampus : an in vivo electrophysiological study. Synapse 1990 / 6 (2) / 175-180.
  • Lista, A. et al, Modulation of the electrically evoked release of 5-(3H)hydroxytryptamine from rat cerebral cortex : effects of alpidem, CL218,872, and diazepam. J. Neurochem. 1988 / 51 (5) / 1414-1421.
  • Yang, X.M. et al, Behavioral evidence for the role of noradrenaline in the putative anxiogenic actions of the inverse benzodiazepine receptor agonist methyl-4-6,7-dimethoxy-beta-carboline-carboxylate. J. Pharmacol. Exp. Ther. 1989 / 250 (1) / 358-363.
  • Ushijiama, I. et al, Cocaine : evidence for NMDA, beta-carboline- and dopaminergic-mediated seizures in mice. Brain. Res. 1998 / 797 (2) / 347-350.
  • Maier, S.F. et al, The dorsal raphe nucleus is a site of action mediating the behavioral effects of the benzodiazepine receptor inverse agonist DMCM. Behav. Neurosci. 1995 / 109 (4) / 759-766.
  • Fanselow, M.S. et al, The benzodiazepine inverse agonist DMCM as an unconditional stimulus for fear-induced analgesia : implications for the role of GABAA receptors in fear-related behaviour. Behav. Neurosci. 1992 / 106 (2) / 336-344.
  • Cutler, M.G. et al, Effects of the benzodiazepine receptor inverse agonist, DMCM, on the behaviour of mice : an ethopharmacological study. Neuropharmacology 1991 / 30 (12A) / 1255-1261.
  • Arora, P.K. et al, Suppression of cytotoxic T lymphocyte (CTL) activity by FG7142, a benzodiazepine receptor 'inverse agonist'. Immunopharmacology 1991 / 21 (2) / 91-97.
  • Petitto, J.M. et al, Suppression of natural killer cell activity by FG7142, a benzodiazepine receptor inverse agonist. Brain. Behav. Immun. 1989 / 3 (1) / 39-46.
  • Arora, P.K. et al, Suppression of the immune response by benzodiazepine receptor inverse agonists. J. Neuroimmunol. 1987 / 15 (1) / 1-9.
  • Marescaux, C. et al, Bidirectional effects of the beta-carbolines in rats with spontaneous petit mal-like seizures. Brain. Res. Bull. 1987 / 19 (3) / 327-335.
  • Jensen, L.H. et al, Bidirectional effects of beta-carbolines and benzodiazepines on cognitive processes. Brain. Res. Bull. 1987 / 19 (3) 359-364.
  • Garginlo, P.A. et al, Is inhibition by diazepam and beta-carbolines of estrogen-induced luteinizing hormone secretion related to sedative effects ? Pharmacol. Biochem. Behav. 1991 / 40 (2) / 335-338.
  • Kreeger, T.J. et al, Diazepam-induced feeding in ceptive grey wolves (Canis Lupus). Pharmacol. Biochem. Behav. 1991 / 39 (3) / 559-561.
  • Cooper, S.J. ,Hyperphagic and anorectic effects of beta-carbolines in a palatable food consumption test : comparisons with triazolam and quazepam. Eur. J. Pharmacol. 1986 / 120 (3) / 257-265.
  • Cooper, S.J. et al, Benzodiazepine receptor ligands and the consumption of highly palatable diet in non-deprived male rats. Psychopharmacology (Berl.) 1985 / 86 (3) / 348-355.
  • Duka, T. et al, Human studies on the benzodiazepine receptor antagonist beta-carboline ZK93426 : antagonism of lormetazepam's psychotropic effects. Psychopharmacology (Berl.) 1988 / 95 (4) / 463-471.
  • Dorow, R. et al, Clinical perspectives of beta-carbolines from first studies in humans. Brain. Res. Bull. 1987 / 19 (3) / 319-326.
  • Duka, T. et al, Effects of ZK93,426, a beta-carboline benzodiazepine receptor antagonist on night sleep pattern in healthy male volunteers. Psychopharmacology (Berl.) 1995 / 117 (2) / 178-185.
  • File, S.E. et al, Actions of the beta-carboline ZK93426 in an animal test of anxiety and the holeboard : interactions with Ro15-1788. J. Neural. Transm. 1986 / 65 (2) / 103-114.
  • Papavergou, E. et al, The evaluation in the ames test of the mutagenicity of tetrahydro-beta-carboline-3-carboxylic acids from smoked foods. Food. Addit. Contam. 1992 / 9 (2) / 183-187.
  • Huttunen, P. et al, Anatomical localization in hippocampus of tetrahydro-beta-carboline-induced alcohol drinking in rat. Alcohol 1987 / 4 (3) / 181-187.
  • Wible, J.H. et al, Cardiovascular effects of beta-carbolines in conscious rats. Hypertens. Res. 1996 / 19 (3) / 161-170.
  • Rovescalli, A.C. et al, Endocrine effects of 5-methoxytryptoline, 5-hydrotryptoline and tryptoline, putative modulators of rat serotonergic system. J. Endocrinol. Invest. 1987 / 10 (1) / 65-72.
  • De Deyn, P.P. et al, Epilepsy and the GABA-hypothesis ,a brief revieuw and some examples. Acta. Neurol. Belg. 1990 / 90 (2) / 65-81.
  • Smythe, G.A. et al, Effects of 6-methoxy-1,2,3,4-tetrahydro-beta-carboline and yohimbine on hypothalamic monoamine status and pituitary hormone release in rats. Aust. J. Biol. Sci. 83 / 36 (4) / 379-386.
  • Wettstein, J.G. et al, Distinctive behavioral effects of the pyrazoloquinoline CGS8216 in squirrel monkeys. Pharmacol. Biochem. Behav. 1988 / 29 (4) / 741-745.
  • Pellow, S. et al, The effects of putative anxiogenic compounds (FG7142, CGS8216 and Ro15-1788) on the rat corticosterone response. Physiol. Behav. 1985 / 35 (4) / 587-590.
  • Deckert, J. et al, CGS8216 treatment decreases central-type benzodiazepine receptors in rat brain. Eur. J. Pharmacol. 1987 / 142 (3) / 457-460.
  • Turteltaub ,K.W. et al, MeIQx-DNA adduct formation in rodent and human tissues at low doses. Mutat. Res. 1997 / 376 (1-2) / 243-252.
  • Hatch, F.T. et al, Quantitative structure-activity (QSAR) relationships of mutagenic aromatic and heterocyclic amines. Mutat. Res. 1997 / 376 (1-2) / 87-96. Blowers, L. et al, Dietary and other lifestyle factors of women with brain gliomas in Los Angeles County. Cancer Causes Control 1997 / 8 (1) / 5-12.
  • Barrett, J.H. et al, Nitrate in drinking water and the incidence of gastric, esophageal, and brain cancer in Yorkshire, England. Cancer Causes Control 1998 / 9 (2) / 153-159.
  • Wang, C.J. et al, Promotional effect of N-nitroso-N-(3keto-1,2-butanediol)-3'-nitrotyramine (a nitrosated Maillard reaction product) in mouse fibroblast cells. Fd. Chem. Toxicol. 1998 / 36 (8) / 631-636.
  • Tseng, T.H. et al, Tumor promoting effect of N-nitroso-N-(2-hexanonyl)-3'-nitrotyramine (a nitrosated Maillard reaction product) in benzo(a)pyrene-initiated mouse skin carcinogenesis. Chem. Biol. Interact. 1998 / 115 (1) / 23-38.
  • De Stefani, E. et al, Dietary nitrosamines ,heterocyclic amines ,and risk of gastric cancer a case-controle study in Uruguay. Nutr. Cancer 1998 / 30 (2) / 158-162.
  • Pfau, W. et al, Identification of the major hepatic DNA adduct formed by the food mutagen 2-amino-9H-pyrido(2,3-b)indole (AalphaC). Chem. Res. Toxicol. 1997 / 10 (10) / 1192-1197.
  • Herneaz, J. et al, Effects of tea and chlorophyllin on the mutagenicity of N-hydroxy-IQ : studies of enzyme inhibition, molecular complex formation ,and degredation / scavenging of the active metabolites. Environ. Mol. Mutagen. 1997 / 30 (4) / 468-474.
  • Kemmerling, W., Toxicity of Palicourea marcgravii : combined effects of fluoracetate, N-methyltyramine and 2-methyl-tetrahydro-beta-carboline. Z. Naturforsch. (C) 1996 / 51 (1-2) / 59-64.
  • Hiramoto, K. et al, Induction of DNA recombination by activated 3-amino-1-methyl-5H-pyrido(4,3-b)indole. Jpn. J. Cancer Res. 1995 / 86 (2) / 155-159.
  • (80) Sugimura, T. et al, Carcinogenic, Mutagenic, and Comutagenic Aromatic Amines in Human Foods. Natl. Cancer Inst. Monogr. 1981 / 58 / 27-33.
  • (81) Raza, H. et al, Metabolism of 2-amino-alpha-carboline. A food borne heterocyclic amine mutagen and carcinogen by human and rodent liver microsomes and by human cytochrome P4501A2. Drug. Metab. Dispos. 1996 / 24 (4) / 395-400.
  • Yoo, M.A. et al, Mutagenic potency of heterocyclic amines in the Drosophila wing spot test and its correlation to carcinogenic potency. Jpn. J. Cancer Res. 1985 / 76 (6) / 468-473.
  • Pfau, W. et al, Characterization of the major DNA adduct formed by the food mutagen 2-amino-3-methyl-9H-pyrido(2,3-b)indole (MeAalphaC) in primary rat hepatocytes. Carcinogenesis 1996 / 17 (12) / 2727-2732.
  • Pfau, W. et al, Pancreatic DNA adducts formed in vitro and in vivo by the food mutagens 2-amino-1-methyl-6-phenylimidazo(4,5-b)prydine (PhIP) and 2-amino-3-methyl-9H-pyrido(2,3-b)indole (MeAalphaC). Mutat. Res. 1997 / 378 (1-2) / 13-22.
  • Ashida, H. et al, Tryptophan pyrolysis products, Trp-P-1 and Trp-P-2 induce apoptosis in primary cultured rat hepatocytes. Biosci. Biotechnol. Biochem. 1998 / 62 (11) / 2283-2287.
  • Sasaki, Y.F. et al, In vivo genotoxicity of heterocyclic amines detected by a modified alkaline single cell gel electrophoresis assay in a multiple organ study in the mouse. Mutat. Res. 1997 / 395 (1) / 57-73.
  • Sugimura,T. et al, Mutagens in food. Journal of Agriculture and Food Chemistry 1995 / 43 / 404-414.
  • Manabe, S. et al, Carcinogenic tryptophan pyrolysis products in the environment. J. Toxicol. Sci. 1991 / 16 (suoppl.1) / 63-72.
  • Higashimoto, M., Inhibitory effects of citrus fruits on the mutagenicity of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid treated with nitrite in the presence of ethanol. Mutat. Res. 1998 / 415 (3) / 219-226.
  • Papavergou, E. et al, The evaluation in the Ames test of the mutagenicity of tetrahydro-beta-carboline-3-carboxylic acids from smoked foods. Food. Addit. Contam. 1992 / 9 (2) / 183-187.
  • Wakabayashi, K. et al, Presence of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acids and tyramine as precursers of mutagens in soyasauce after nitrite treatment. IARC Sci. Publ. 1984 / 57 / 17-24.
  • Hammons, G.J. et al, Effects of chemoprotective agents on the metabolic activation of the carcinogenic arylamines PhIP and 4-aminobiphenyl in human and rat liver microsomes. Nutr. Cancer 199 / 33 (1) / 46-52.ï¿¿
  • Sabbioni, G. et al, Hemoglobin binding of bicyclic aromatic amines. Chem. Res. Toxicol. 1998 / 11 (5) / 471-483.
  • Williams, G.M. et al, Inhibition by acetaminophen of intestinal cancer in rats induced by an aromatic amine similar to food mutagens. Eur. J. Cancer Prev. 1997 / 6 (4) / 357-362.
  • Pence, B.C. et al, Feeding of a well-cooked beef diet containing a high heterocyclic amine content enhances colon and stomach carcinogenesis in 1,2-dimethylhydrazine-treated rats. Nutr. Cancer 1998 / 30 (3) / 220-226.
  • Hiramoto, K. et al, Induction of DNA recombination by activated 3-amino-1-methyl-5H-pyrido(4,3-b)indole. Jpn. J. Cancer Res. 1995 / 86 (2) / 155-159.
  • Ojala, W.H. et al, Heterocyclic N-acetoxyarylamines, models for the putative ultimate carcinogens of aromatic amines : 2-acetoxyamino-5-phenylpyridine and 2-acetoxyaminopyridine. Acta. Cristallogr. C. 1997 / 53 (pt 5) / 634-637.
  • Koch, W.H. et al, Specificity of base substitution mutations induced by the dietary carcinogens 2-amino-1methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) and 2-amino-3-methylimidazo(4,5-f)quinoline (IQ) in Salmonella. Environ. Mol. Mutagen 1998 / 31 (4) / 327-332.
  • Nagao, M. et al, Genetic changes induced by heterocyclic amines. Mutat. Res. 1997 / 376 (1-2) / 161-167.
  • Thompson, L.H. et al, Comparative genotoxic effects of the cooked-food-related mutagens Trp-P-2 and IQ in bacteric and cultured mammalian cells. Mutat. Res. 1983 / 117 (3-4) / 243-257.
  • Broschard, T.H. et al, Mutagenic specificity of the food mutagen 2-amino-3-methylimidazo(4,5-f)quinoline in Escheria coli using the yeast URA3 gene as a target. Carcinogenesis 1998 / 19 (2) / 305-310.
  • Waldren, C.A. et al, Mutant yields and mutational spectra of the heterocyclic amines MeIQ and PhIP at the si locus of human-hamster AL cells with activation by chick embryo liver (CELC) co-cultures. Mutat. Res. 1999 / 425 (1) / 29-46.
  • Okonogi, H. et al, Agreement of mutational characteristics of heterocyclic amines in lacl of the Big Blue mouse with those in tumor related genes in rodents. Carcinogenesis 1997 / 18 (4) / 745-748.
  • (95) Sasaki, Y.F. et al, Colon specific genotoxicity of heterocyclic amines detected by themodified alkaline single cell gel electrophoresis assay of multiple mouse organs. Mutat. Res. 1998 / 414 (1-3) / 9-14.
  • Grivas, S., Synthetic roots to the food carcinogen 2-amino-3,8-dimethylimidazo(4,5-f)quinozaline (8-MeIQx) and related compounds. Princess Takamatsu Symp. 1995 / 23 / 1-8.
  • Schut, H.A. et al, DNA adducts of heterocyclic amine food mutagens : implications for mutagenesis and carcinogenesis. Carcinogenesis 1999 / 20 (3) / 353-368.
  • Frandsen, H. ,Excretion of DNA adducts of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine and and 2-amino-3,4,8-trimethylimidazo(4,5-f)quinoxaline, PhIP-dg, PhIP-DNA and DiMeIQx-DNA from rat. Carcinogenesis 1997 / 18 (8) / 1555-1560.
  • Knize, M.G. et al, Identification of the mutagenic quinoxaline isomers from fried ground beef. Mutat. Res. 1987 / 178 (1) / 25-32.
  • Solyakov, A. et al, Heterocyclic amines in process flavours, process flavour ingredients, bouillon concentrates and a pan residue. Food Chem. Toxicol. 1999 / 37 (1) / 1-11.
  • Skog, K. et al, Analysis of nonpolar heterocyclic amines in cooked foods and meat extracts using gas chromatography-mass spectometry. J. Chromatogr. A. 1998 / 803 (1-2) / 227-233. , Stavric, B. et al, Mutagenic heterocyclic aromatic amines (HAA's) in 'processed food flavour' samples. Food Chem. Toxicol. 1997 / 35 (2) / 185-197. , Wakabayashi, K. et al, Human exposure to mutagenic / carcinogenic heterocyclic amines and comutagenic beta-carbolines. Mutat. Res. 1997 / 376 (1-2) / 253-259. , Galceran, M.T. et al, Determination of heterocyclic amines by pneumatically assisted electrospray liquid chromatography-mass spectometry. J. Chromatogr. A. 1996 / 730 (1-2) / 185-194.
  • Gross, G.A. et al, Heterocyclic aromatic amine formation in grilled bacon, beef and fish and in grilled scrapings. Carcinogenesis 1993 / 14 (11) / 2313-2318.
  • Sugimura, T. et al, Mutagenic factors in cooked foods. Crit. Rev. Toxicol. 1979 / 6 (3) / 189-209.
  • Becher, G. et al, Isolation and identification of mutagens from a fried Norwegian meat product. Carcinogenesis 1988 / 9 (2) / 247-253.
  • Overvik, E. et al, Influence of creatine, amino acids and water on the formation of the mutagenic heterocyclic amines found in cooked meat. Carcinogenesis 1989 / 10 (12) / 1293-1301.
  • Wakabayashi, K. et al, Identification of new mutagenic heterocyclic amines and quantification heterocyclic amines. Princess Takamatsu Symp. 1995 / 23 / 39-49.
  • Vikse, R. et al, Heterocyclic amines in cooked meat (in Norwegian). Tidsskr. Nor. Laegeforen 1999 / 119 (1) / 45-49.
  • (Takahashi, T. et al, Uptake of neurotoxic candidate, (R)-1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline into human dopaminergic neuroblastoma 3H-SY5Y cells by dopamine transportsystem. J. Neural. Transm. Gen. Sect. 1994 / 98 (2) / 107-118.
  • Mandir, A.S. et al, Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Proc. Natl. Acad. Sci. U.S.A. 1999 / 96 (10) / 5774-5779. , Harik, S.I. et al, On the mechanisms underlying 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity : the effect of perinigral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, its metabolite and their analogues in the rat. J. Pharmacol. Exp. ther. 1987 / 241 (2) / 669-676.
  • Frei, B. et al, N-methyl-4-phenylpyridinium (MPP+) together with 6-hydroxydopamine or dopamine stimulates Ca2+ release from mitochondria. FEBS Lett. 1986 / 198 (1) / 99-102.
  • Heikkila, R.E. et al, Prevention of MPTP-induced neurotoxicity by AGN-1133 and AGN-1135, selective inhibitors of monoamine oxidase-B. Eur. J. Pharmacol. 1985 / 116 (3) / 313-317.
  • Heikkila, R.E. et al, Dopaminergic neurotoxicity of rotenone and the 1-methyl-4-phenylpyridinium ion after their stereotaxic administration to rats : implication for the mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity. Neurosci. Lett. 1985 / 62 (3) / 389-394.
  • Mytilineou, C. et al, 1-methyl-4phenylpyridine (MPP+) is toxic to mesencephalic dopamine neurons in culture. Neurosci. Lett. 1985 / 57 (1) / 19-24.
  • Matsubara, K. et al, Endogenously occurring beta-carboline induces parkinsonism in non primate animals : a possible causative protoxin in idiopathic Parkinson's Disease. J. Neurochem. 1998 / 70 (2) / 727-735.
  • Fonne-Pfister, R. et al, MPTP, the neurotoxin inducing Parkinson's disease, is a potent competitive inhibitor of human and rat cytochrome P450 isozymes (P450buf1, P450db1) catalyzing debrisoquine 4-hydroxylation. Biochem. Biophys. Res. Commun. 1987 / 148 (3) / 1144-1150.
  • Naoi, M. et al, Metabolism of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in a rat pheochromocytoma cell line, PC12h. Life Sci. 1987 / 41 (24) / 2655-2661.
  • Heikkila, R.E. et al, Studies on the oxidation of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine by monoamine oxidase B. J. Neurochem. 1985 / 45 (4) / 1049-1054.
  • Fuller, R.W. et al, Mechanisms of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity to striatal dopamine neurons in mice. Prog. Neuropsychopharmacol. Biol. Psychiatry 1985 / 9 (5-6) / 687-690.
  • Heikkila, R.E. et al, Protection against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine by MAO inhibitors. Nature 1984 / 311 (5985) / 467-469
  • Pai, K.S. et al, Protection and potentiation of MPTP-induced toxicity by cytochrome P450 inhibitors and inducer : in vitro studies with brain slices. Brain. Res. 1991 / 555 (2) / 239-244.
  • Shahi, G.S. et al, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity : partial protection against striato-nigral dopamine sepletion in C57BL/6J mice by cigarette smoke exposure and by beta-naphthoflavone-pretreatment. Neurosci. Lett. 1991 / 127 (2) / 247-250.
  • Melamed, E. et al, Dopamine, but not norepinephrine or serotonine uptake inhibitors protect mice against neurotoxicity of MPTP. Eur. J. Pharmacol. 1985 / 116 (1-2) / 179-181.
  • Heikkila, R.E. et al, Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse : relationships between monoamine oxidase, MPTP metabolism and neurotoxicity. Life Sci. 1985 / 36 (3) / 231-236.
  • Melamed, E. et al, Mesolimbic dopaminergic neurons are not spared by MPTP neurotoxicity in mice. Eur. J. Pharmacol. 1985 / 114 (1) / 97-100.
  • Wilson, J.A. et al, MPTP causes a non-reversible depression of synaptic transmission in mouse neostriatal brain slice. Brain Res. 1986 / 368 (2) / 357-360.
  • Wu, W.R. et al, Involvement of monoamine oxidase inhibition in neuroprotective and neurorestorative effects of Ginkgo biloba extract against MPTP-induced nigrostriatal dopaminergic toxicity in C57 mice. Life Sci. 1999 / 65 (2) / 157-164.
  • Pileblad, E. et al, Catecholamine-uptake inhibitors prevents the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) in mouse brain. Neuropharmacology 1985 / 24 (7) / 689-692.
  • Gerhardt, G. et al, Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse : an in vivo electrochemical study. J. Pharmacol. Exp. Ther. 1985 / 235 (1) / 259-265.
  • Lee, E.H. et al, Comparitive studies of the neurotoxicity of MPTP in rats. Chin. J. Physiol. 1992 / 35 (4) / 317-336.
  • Hara, K. et al, Reversible serotinergic neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mouse striatum studied byneurochemical and immunohistochemical approaches. Brain Res. 1987 / 410 (2) / 371-374.
  • Malgrange, B. et al, beta-Carbolines induce apoptotic death of cerebellar granule neurones in culture. Neuroreport 1996 / 7 (18) / 3041-3045.
  • Perry, T.L. et al, 4-Phenylpyridine and three other analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine lack dopaminergic nigrostriatal neurotoxicity in mice and marmosets. Neurosci. Lett. 1987 / 75 (1) / 65-70.
  • Harris, C.A. et al, Modulation of striatal quinolinate neurotoxicity by elevation of endogenous brain kynurenic acid. Br. J. Pharmacol. 1998 / 124 (2) / 391-399.
  • Levivier, M. et al, Quinolinic acid-induced lesions of the rat striatum : quantitative autoradiographic binding assessment. Neurol. Res. 1998 / 20 (1) / 46-56.
  • Pai, K.S. et al, Quisqualic-acid-induced neurotoxicity is protected by NMDA and non-NMDA antagonists. Neurosci. Lett. 1992 / 143 (1-2) / 177-180.
  • Zinkand, W.C. et al, Quisqualate neurotoxicity in rat cortical cultures : pharmacology and mechanisms. Eur. J. Pharmacol. 1992 / 648 / 355-357.
  • Nagatsu, Isoquinoline neurotoxics in the brain and Parkinson's disease. Neurosci. Res. 1997 / 29 (2) / 99-111.
  • Naoi, M. et al, Dopamine-derived endogenous 1(R), 2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, N-methyl-(R)-salsolinol, induced parkinsonism in rat : biochemical ,pathological and behavioral studies. Brain. Res. 1996 / 709 (2) / 285-295.
  • Naoi, M. et al, Enzymatic oxidation of the dopaminergic neurotoxin 1(R), 2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, into 1,2(N)-dimethyl-6,7-dihydroxyisoquinolinium ion. Life Sci. 1995 / 57 (11) / 1061-1066.
  • Maruyama, W. et al, N-methyl(R)salsolinol produces hydroxyl radicals : involvement to neurotoxicity. Free Radic. Biol. Med. 1995 / 19 (1) / 67-75.
  • McNaught, K.S. et al, Inhibition of complex 1 by isoquinoline derivates structurally related to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Biochem. Pharmacol. 1995 / 50 (11) / 1903-1911.
  • Skaper, S.D. et al, Characterization of 2,3,4-trihydroxyphenylalanine neurotoxicity in vitro and protective effects of ganglioside GM1 : implications for Parkinson's disease. J. Pharmacol. Exp. ther. 1992 / 263 (3) / 1440-1446.
  • Dodel, R.C. et al, Caspase-3-like proteases and 6-hydroxydopamine-induced neuronal cell death. Brain. Res. Mol. Brain. Res. 1999 / 64 (1) / 141-148.
  • Double, K.L. et al, In vitro studies of ferritin iron release and neurotoxicity. J. Neurochem. 1998 / 70 (6) / 2492-2499.
  • Javitch, J.A. et al, Parkinsononism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-pyridine : characterization and localization of receptor binding in sites in rat and human brain. Proc. Natl. Acad. Sci. U.S.A. 1984 / 81 (14) / 4591-4595.
  • Hallman, H. et al, Neurotoxicity of the meperidine analogue N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on brain catecholamine neurons in the mouse. Eur. J. Pharmacol. 1984 / 97 (1-2) / 133-136.
  • Irwin, I. et al, Selective accumulation of MPP+ in the substantia nigra : a key to neurotoxicity ? Life Sci. 1985 / 36 (3) / 207-212.
  • Cohen, G. et al, Pargyline and deprenyl prevent the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in monkeys. Eur. J. Pharmacol. 1984 / 106 (1) / 209-210.
  • Markey, S.P. et al, Intraneuronal generation of a pyridinium metabolite may cause drug-induced parkinsonism. Nature 1984 / 311 (5985) / 464-467. , Burns, R.S. et al, The neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the monkey and man. Can. J. Neurol. Sci. 1984 / 11 (1 suppl.) / 166-168.
  • Heikkila, R.E. et al, Protection against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine by MAO inhibitors. Nature 1984 / 311 (5985) / 467-469.
  • Ramsay, R.R. et al, Inhibition of NADH oxidation by pyridine derivates. Biochem. Biophys. Res. Commun. 1987 / 146 (1) / 53-60.
  • Ansher, S.S. et al, Role of N-methyltransferases in the neurotoxicity associated with the metabolites of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and other 4-substituted pyridines present in the environment. Biochem. Pharmacol. 1986 / 35 (19) / 3359-3363.
  • Deutch, A.Y. et al, 3-Acetylpyridine-induced degeneration of the nigrostriatal dopamine system : an animal model of olivopontocerebellar atrophy-associated parkinsonism. Exp. Neurol. 1989 / 105 (1) / 1-9.
  • Trevor, A.J. et al, Bioactivity of MPTP : reactive metabolites and possible biochemical sequelae. Life Sci. 1987 / 40 (8) / 713-719.
  • Youngster, S.K. et al, 1-Methyl-4-cyclohexyl-1,2,3,6-tetrahydropyridine (MCTP) : an alicyclic MPTP-like neurotoxin. Neurosci. Lett. 1987 / 79 (1-2) / 151-156.
  • Kindt, Role for monoamine oxidase-A (MAO-A) in the bioactivation and nigrostriatal dopaminergic neurotoxicity of the MPTP analog, 2'-Me-MPTP. Eur. J. Pharmacol. 1988 / 146 (2-3) / 313-318.
  • Sonsalla, P.K. et al, Characteristics of 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine-induced neurotoxicity in the mouse. J. Pharmacol. Exp. Ther. 1987 / 242 (3) / 850-857.
  • Heikkila, R.E. et al, Importance of monoamine oxidase in the bioactivation of neurotoxic analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc. Natl. Acad. Sci. U.S.A. 1988 / 85 (16) / 6172-6176.
  • Youngster, S.K. et al, Evaluation of the biological activity of several analogs of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. J. Neurochem. 1987 / 48 (3) / 929-934.
  • Finnegan, K.T. et al, 1,2,3,6-tetrahydro-1-methyl-4-(methylpyrrol-2-yl)pyridine : studies on the mechanism of action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. J. Pharmacol. Exp. Ther. 1987 / 242 (3) / 1144-1151.
  • Chiueh, C.C. et al, Enhanced hydroxyl radical generation by 2'-methyl analog of MPTP : suppression by clorgyline and deprenyl. Synapse 1992 / 11 (4) / 346-348.
  • Desole, M.S. et al, Correlation between 1-methyl-4-phenylpyridinium (MPP+) levels, ascorbic acid oxidation and glutathione levels in the striatal synaptosomes of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated rats. Neurosci. Lett. 1993 / 161 (2) / 121-123.
  • Mihatsch, W. et al, Treatment with antioxidants does not prevent loss of dopamine in the striatum of MPTP-treated common marmosets : preliminary observations. J. Neural. Transm. Park. Dis. Dement. Sect. 1991 / 3 (1) / 73-78.
  • Sutphin, M.S. et al, Effects of low selenium diets on antioxidant status and MPTP toxicity in mice. Neurochem. Res. 1991 / 16 (12) / 1257-1263.
  • Gong, L. et al, Vitamine E supplements fail to protect mice from acute MPTP neurotoxicity. Neuroreport. 1991 / 2 (9) / 544-546.

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