Metabolism of the food-borne mutagen 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline in humans

Chemical Research in Toxicology

Volumn 11, Issue 3, 1998, Pages 217-225

  Turesky, Robert J ^a   Garner, R Colin ^b   Welti, Dieter H ^a   Richoz, Janique ^a   Leveson, Steve H ^c   Dingley, Karen H ^b,d   Turteltaub, Kenneth W ^d   Fay, Laurent B ^a  

^a NESTLÉ RESEARCH CENTER   (Switzerland)

^b UNIVERSITY OF YORK   (United Kingdom)

^c YORK HOSPITAL   (United Kingdom)

^d LAWRENCE LIVERMORE NATIONAL LABORATORY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 3,8 DIMETHYLIMIDAZO[4,5 F]QUINOXALINE; 2N (BETA 1 GLUCOSIDURONYL) N HYDROXY 2 AMINO 3,8 DIMETHYLIMIDAZO[4,5 F]QUINOOXALINE; AROMATIC AMINE; CYTOCHROME P450; HETEROCYCLIC AMINE; MUTAGENIC AGENT; QUINOXALINE DERIVATIVE; UNCLASSIFIED DRUG;

ADULT; AGED; AMINO ACID METABOLISM; AMINO ACID URINE LEVEL; ARTICLE; CARCINOGENESIS; CARIOGENIC DIET; CLINICAL ARTICLE; COOKING; FEMALE; FOOD PROCESSING; HUMAN; HUMAN TISSUE; IMMUNOAFFINITY CHROMATOGRAPHY; LIVER MICROSOME; LONG TERM EXPOSURE; MALE; MEAT; METABOLITE; MUTAGENIC ACTIVITY; ULTRAVIOLET SPECTROSCOPY; URINE LEVEL;

ADMINISTRATION, ORAL; AGED; AGED, 80 AND OVER; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; FEMALE; FOOD CONTAMINATION; HUMANS; MALE; MICROSOMES, LIVER; MIDDLE AGED; MUTAGENS; QUINOXALINES; REFERENCE STANDARDS; SMOKING;

PRIMATES; RODENTIA;

EID: 0031938642     PISSN: 0893228X     EISSN: None     Source Type: Journal    
DOI: 10.1021/tx9701891     Document Type: Article

References (53)

1. Felton, J. S., and Knize, M. G. (1990) Heterocyclic amine mutagens/carcinogens in foods. In Handbook of Experimental Pharmacology (Cooper, C. S., and Grover, P. L., Eds.) pp 471-502, Springer-Verlag, Berlin, Heidelberg.
2. Gross, G. A., Turesky, R. J., Fay, L. B., Stillwell, W. G., Skipper, P. L., and Tannenbaum, S. R. (1993) Heterocyclic aromatic amine formation in grilled bacon, beef and fish and in grill scrapings. Carcinogenesis 14, 2313-2318.
3. Wakabayashi, K., Nagao, M., Esumi, H., and Sugimura, T. (1992) Food-derived mutagens and carcinogens. Cancer Res. 52 (Suppl.), 2092s-2098s.
4. Sugimura, T., and Nagao, M. (1993) Carcinogenic factors in food with relevance to colon cancer development. Mutat. Res. 290, 43-51.
5. Murray, S., Gooderham, N. J., Boobis, A. R., and Davies, D. S. (1988) Measurement of MeIQx and DiMeIQx in fried beef by capillary column gas chromatography electron capture negative ion chemical ionisation mass spectrometry. Carcinogenesis 9, 321-325.
6. Sinha, R., Rothman, N., Brown, E. D., Mark, S. D., Hoover, R. N., Caporaso, N. E., Levander, O. A., Knize, M. G., Lang, N. P., and Kadlubar, F. F. (1994) Pan-fried meat containing high levels of heterocyclic aromatic amines but low levels of polycyclic aromatic hydrocarbons induces cytochrome P4501A2 activity in humans. Cancer Res. 54, 6154-6159.
7. Doll, R., and Peto, R. (1981) The causes of cancer: Quantitative estimates of avoidable risks of cancer in the United States today. J. Natl. Cancer Inst. 66, 1191-1308.
8. Schiffman, M. H., and Felton, J. S. (1990) Letter to the editor: Re: "Fried foods and the risk of colon cancer" Am. J. Epidemiol. 131, 376-378.
9. Willet, W. C., Stampger, M. J., Graham, A., Colditz, G. A., Rosner, B. A., and Speizer, F. E. (1990) Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women. N. Engl. J. Med. 323, 1664-672.
10. Gerhardsson de Verdier, M., Hagman, U., Peters, R. K., Steineck, G., and Övervik, E. (1991) Meat, cooking methods and colorectal cancer: A case-referent study in Stockholm. Int. J. Cancer 49, 520-525.
11. Muscat, J. E., and Wynder, E. L. (1994) The consumption of well-done red meat and the risk of colorectal cancer. Am. J. Public Health 84, 856-858.
12. Giovannucci, E., Rimm, E. B., Stampfer, M. J., Colditz, G. A., Ascherio, A., and Willett, W. C. (1994) Intake of fat, meat, and fiber in relation to risk of colon cancer in men. Cancer Res. 54, 2390-2397.
13. Hayatsu, H., Kasai, H., Yokoyama, S., Miyazawa, T., Yamaizumi, Z., Sato, S., Nishimura, S., Arimoto, S., Hayatsu, T., and Ohara, Y. (1987) Mutagenic metabolites in urine and feces of rats fed with 2-amino-3,8-dimethylirnidazo[4,5-f]quinoxaline, a carcinogenic mutagen present in cooked meat. Cancer Res. 47, 791-794.
14. Turesky, R. J., Aeschbacher, H. U., Würzner, H. P., Skipper, P. L., and Tannenbaum, S. R. (1988) Major routes of metabolism of the food-borne carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline in the rat. Carcinogenesis 9, 1043-1048.
15. Sjödin, P., Wallin, H., Alexander, J. A., and Jägerstad, M. (1989) Disposition and metabolism of the food mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in rats. Carcinogenesis 10, 1269-1275.
16. Turesky, R. J., Bracco-Hammer, I., Markovic, J., Richli, U., Kappeler, A.-M., and Welti, D. H. (1990) The contribution of N-oxidation to the metabolism of the food-borne carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in rat hepatocytes. Chem. Res. Toxicol. 3, 524-535.
17. Turesky, R. J., Markovic, J., Bracco-Hammer, I., and Fay, L. B. (1991) The effect of dose and cytochrome P450 induction on the metabolism and disposition of the food-borne carcinogen 2-amino-3,8-dimethylimidazo[4, 5-f]quinoxaline. Carcinogenesis 12, 1847-1855.
18. Snyderwine, E. G., Welti, D. H., Davis, C. D., Fay, L. B., and Turesky, R. J. (1995) Metabolism of the food-derived carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in nonhuman primates. Carcinogenesis 16, 1377-1384.
19. Kato, R. (1986) Metabolic activation of mutagenic heterocyclic aromatic amines from protein pyrolysates. CRC Crit. Rev. Toxicol. 16, 307-348.
20. Yamazoe, Y., Abu-Zeid, M., Manabe, S., Toyama, S., and Kato, R. (1988) Metabolic activation of a protein pyrolysate promutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline by rat liver microsomes and purified cytochrome P-450. Carcinogenesis 9, 105-109.
21. 2 atoms of guanine. Chem. Res. Toxicol. 5, 479-490.
22. Yamazoe, Y., Abu-Zeid, M., Yamauchi, K., and Kato, R. (1988) Metabolic activation of pyrolysate arylamines by human liver microsomes; possible involvement of a P-448-H type cytochrome P-450. Jpn. J. Cancer Res. (Gann) 79, 1159-1167.
23. Turesky, R. J., Lang, N. P., Butler, M. A., Teitel, C. H., and Kadlubar, F. F. (1991) Metabolic activation of carcinogenic heterocyclic aromatic amines by human liver and colon. Carcinogenesis 12, 1839-1845.
24. Rich, K. J., Murray, B. P., Lewis, I., Rendell, N. B., Davies, D. S., Gooderham, N. J., and Boobis, A. R. (1992) N-Hydroxy-MeIQx is the major microsomal oxidation product of the dietary carcinogen MeIQx with human liver. Carcinogenesis 13, 2221-2226.
25. Chou, H.-C., Lang, N. P., and Kadlubar, F. F. (1995) Metabolic activation of N-hydroxy arylamines and N-hydroxy heterocyclic amines by human sulfotransferase(s). Cancer Res. 55, 525-529.
26. Minchin, R. F., Reeves, P. T., Teitel, C. H., McManus, M. E., Mojarrabi, B., Ilett, K. F., and Kadlubar, F. F. (1992) N- and O-acetylation of aromatic and heterocyclic amine carcinogens by human monomorphic and polymorphic acetyltransferases expressed in COS-1 cells. Biochem. Biophys. Res. Commun. 185, 839-844.
27. Ushiyama, H., Wakabayashi, K., Hirose, M., Itoh, H., Sugimura, T., and Nagao, M. (1991) Presence of carcinogenic heterocyclic amines in urine of healthy volunteers eating normal diet, but not of inpatients receiving parenteral alimentation. Carcinogenesis 12, 1417-1422.
28. Lynch, A. M., Knize, M. G., Boobis, A. R., Gooderham, N., Davies, D. S., and Murray, S. (1992) Intra- and interindividual variability in systemic exposure in humans to 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine, carcinogens present in food. Cancer Res. 52, 6216-6223.
29. Stillwell, W. G., Turesky, R. J., Gross, G. A., Skipper, P. L., and Tannenbaum, S. R. (1994) Human urinary excretion of sulfamate and glucuronide conjugates of 2-amino-3,8-dimethylimdazo[4,5-b]quinoxaline (MeIQx). Cancer Epidemiol. Biomarkers Prevention 3, 399-405.
30. Boobis, A. R., Lynch, A. M., Murray, S., de la Torre, R., Solans, A., Farré, M., Segura, J., Gooderham, N. J., and Davies, D. S. (1994) CYP1A2-catalyzed conversion of dietary heterocyclic amines to their proximate carcinogens is their major route of metabolism in humans. Cancer Res. 54, 89-94.
31. Stillwell, W. G., Kidd, L. C., Wishnok, J. S., Tannenbaum, S. R., and Sinha, R. (1997) Urinary excretion of unmetabolized and phase II conjugates of 2-arnino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3,8- dimethylimidazo[4,5-f]quinoxaline in humans: Relationship to cytochrome P450 1A2 and N-acetyl-transferase activity. Cancer Res. 57, 3457-3464.
32. Sinha, R., Rothman, N., Brown, E. D., Salmon, C. P., Knize, M. G., Swanson, C. S., Rossi, S. C., Mark, S. D., Levander, O. A., and Felton, J. S. (1995) High concentrations of the carcinogen 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) occur in chicken but are dependent on the cooking method. Cancer Res. 55, 4516-4519.
33. Turesky, R. J., Forster, C. M., Aeschbacher, H. U., Würzner, H. P., Skipper, P. L., Trudel, L. J., and Tannenbaum, S. R. (1989) Purification of the food-borne carcinogens 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethlyimidazo[4,5-f]quinoxaline in heated meat products by immunoaffinity chromatography. Carcinogenesis 10, 151-56.
34. Shimada, T., Iwasaki, M., Martin, M. V., and Guengerich, F. P. (1989) Human liver microsomal cytochrome P-450 enzymes involved in the bioactivation of procarcinogens detected by umu gene response in Salmonella typhimurium TA 1535/pSK1002. Cancer Res. 49, 3218-3228.
35. Fay, L. B., and Turesky, R. J. (1992) Electron impact and fast atom bombardment mass spectrometric analysis of the food-borne carcinogens 2-amino-3-methylimidazo[4,5-f]quinoline, 2-amino-3,8-dimethlyimidazo[4,5-f]quinoxaline and their metabolites. Biol. Mass Spectrom. 21, 463-469.
36. Guengerich, F. P., and Shimada, T. (1991) Oxidation of toxic and carcinogenic chemicals by human cytochrome P-450 enzymes. Chem. Res. Toxicol. 4, 391-407.
37. Gonzalez, F. J., and Gelboin, H. V. (1994) Role of human cytochrome P450 in the metabolic activation of chemical carcinogens and toxins. Drug Metab. Disp. 26, 165-183.
38. Schweikl, H., Taylor, J. A., Kitareewan, S., Linko, P., Nagorney, D., and Goldstein, J. A. (1993) Expression of CYP1A1 and CYP1A2 genes in human liver. Pharmacogenetics 3, 239-249.
39. 32P-postlabeling method, in the liver of rats fed MeIQx. Carcinogenesis 24, 2165-2170.
40. 2-(deoxyguanosin-8-yl)-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (dG.-C8-MeIQx) in human tissues. Carcinogenesis 17, 1029-1034.
41. Kadlubar, F. F., Butler, M. A., Kaderlik, K. R., Chou, H.-C., and Lang, N. P. (1992) Polymorphisms for aromatic amine metabolism in humans: Relevance for human carcinogenesis. Environ. Health Perspect. 98, 69-74.
42. Snyderwine, E. G., Welti, D. H., Fay, L. B., Würzner, H. P., and Turesky, R. J. (1992) Metabolism of the food-mutagen 2-amino-3-methylimidazo[4,5-f]quinoline in nonhuman primates undergoing carcinogen bioassay. Chem. Res. Toxicol. 5, 843-851.
43. Kaderlik, K. R., Mulder, G. J., Turesky, R. J., Lang, N. P., Teitel, C. H., Chiarelli, M. P., and Kadlubar, F. F. (1994) Glucuronidation of N-hydroxy heterocyclic amines by human and rat liver microsomes. Carcinogenesis 15, 1695-1701.
44. Ilett, K. F., David, B. M., Detchon, P., Castleden, W. M., and Kwa, R. (1987) Acetylation phenotype in colorectal carcinoma. Cancer Res. 47, 1466-1469.
45. Eaton, D. L., Gallagher, E. P., Bammler, T. K., and Kunze, K. L. (1995) Role of cytochrome P4501A2 in chemical carcinogenesis: implications for human variability in expression and enzyme activity. Pharmacogenetics 5, 259-274.
46. Robert-Thomson, I. C., Ryan, P., Khoo, K. K., Hart, W. J., McMichael, A. J., and Butler, R. N. (1996) Diet, acetylator phenotypes, and risk of colorectal neoplasia. Lancet 347, 1372-1374.
47. Lang, N. P., Butler, M. A., Massengill, J., Lawson, M., Stotts, R. C., Hauer-Jensen, M., and Kadlubar, F. F. (1994) Rapid metabolic phenotypes for acetyltransferase and cytochrome P4501A2 and putative expsoure to food-borne heterocyclic mines increase the risk for colorectal cancer or polyps. Cancer Epidemiol. Biomarkers Prevention 3, 675-682.
48. Butler, M. A., Guengerich, F. P., and Kadlubar, F. F. (1989) Metabolic oxidation of the carcinogens 4-aminobiphenyl and 4,4′-methylenebis(2-chloroaniline) by human hepatic microsomes and by purified rat hepatic cytochrome P-450 monooxygenases. Cancer Res. 49, 25-31.
49. Butler, M. A., Lang, N. P., Young, J. F., Caporaso, N. E., Vineis, P., Hayes, R. B., Teitel, C. H., Massengill, J. P., Lawsen, M. F., and Kadlubar, F. F. (1992) Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites. Pharmacogenetics 2, 116-127.
50. Vistisen, K., Poulsen, H. E., and Loft, S. (1992) Foreign compund metabolism capacity in man measured from metabolites of dietary caffeine. Carcinogenesis 13, 1561-1568.
51. Alvares, A. P., Kappas, A., Eiseman, J. L., Anderson, K. E., Pantuck, C. B., Pantuck, E. J., Hsiao, K. C., Garland, W. A., and Conney, A. H. (1979) Intel-individual variation in drug metabolism. Clin. Pharmacol. Ther. 26, 407-419.
52. Layton, D. W., Bogen, K. T., Knize, M. G., Hatch, F. T., Johnson, V. M., and Felton, J. S. (1995) Cancer risk of heterocyclic amines in cooked foods: An analysis and implications for research. Carcinogenesis 16, 39-52.
53. Bogen, K. T. (1994) Cancer potencies of heterocyclic amines found in cooked foods. Food Chem. Toxicol. 32, 505-515.