N-oxidative metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in humans: Excretion of the N2-glucuronide conjugate of 2- hydroxyamino-MeIQx in urine

Cancer Research

Volumn 59, Issue 20, 1999, Pages 5154-5159

  Stillwell, W G ^a   Turesky, Robert J ^b   Sinha, Rashmi ^c   Tannenbaum, Steven R ^a  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^b NESTLÉ RESEARCH CENTER   (Switzerland)

^c NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 3,8 DIMETHYLIMIDAZO[4,5 F]QUINOXALINE; ACETIC ACID; ACYLTRANSFERASE; CYTOCHROME P450; GLUCURONIDE; GLUCURONOSYLTRANSFERASE; HYDROXYLAMINE;

ARTICLE; CARCINOGENESIS; CONTROLLED STUDY; ENZYME ACTIVITY; GENOTOXICITY; GLUCURONIDATION; HUMAN; MEAT; MUTAGENICITY; NORMAL HUMAN; PRIORITY JOURNAL; URINARY EXCRETION;

ARYLAMINE N-ACETYLTRANSFERASE; BIOTRANSFORMATION; CARCINOGENS; CYTOCHROME P-450 CYP1A2; HUMANS; HYDROXYLAMINES; MUTAGENS; OXIDATION-REDUCTION; PHENOTYPE; QUINOXALINES;

EID: 0032741512     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (42)

1. Felton, J. S., and Knize, M. G. Heterocyclic-amine mutagens/carcinogens in foods. In: C. S. Cooper and P. L. Grover (eds.), Handbook of Experimental Pharmacology, pp. 471-502. Berlin: Springer-Verlag, 1990.
2. Wakabayashi, K., Ushiyama, H., Takahashi, M., Nukaya, H., Kim, S., Hirose, M., Ochiai, M., Sugimura, T., and Nagao, M. Exposure to heterocyclic amines. Environ. Health Perspect., 99: 129-133, 1993.
3. Layton, D. W., Bogen, K. T., Knize, M. G., Hatch, F. T., Johnson, V. M., and Felton, J. S. Cancer risk of heterocyclic amines in cooked foods: an analysis and implications for research. Carcinogenesis (Lond.), 16: 39-52, 1995.
4. Stavric, B. Biological significance of trace levels of mutagenic heterocyclic aromatic amines in human diet: a critical review. Food Chem. Toxicol., 32: 977-994, 1994.
5. Yamazoe, Y., Abu-Zeid, M., Manabe, S., Toyama, S., and Kato, R. 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 (Lond.), 9: 105-109, 1988.
6. Rich, K. J., Murray, B. P., Lewis, I., Rendell, N. B., Davies, D. S., Gooderham, N. J., and Boobis, A. R. N-Hydroxy-MeIQx is the major microsomal oxidation product of the dietary carcinogen MeIQx with human liver. Carcinogenesis (Lond.), 13: 2221-2226, 1992.
7. Turesky, R. J., Constable, A., Richoz, J., Varga, N., Markovic, J., Martin, M. V., and Guengerich, F. P. Activation of heterocyclic aromatic amines by rat and human liver microsomes and by purified rat and human cylochrome P450 IA2. Chem. Res. Toxicol., 11: 925-936, 1998.
8. Kato, R., and Yamazoe, Y. Metabolic activation and covalent binding to nucleic acids of carcinogenic heterocyclic amines from cooked foods and amino acid pyrolysates. Jpn. J. Cancer Res., 78: 297-311, 1987.
9. Turesky, R. J., Lang, N. P., Butler, M. A., Teitel, C. H., and Kadlubar, F. F. Metabolic activation of carcinogenic heterocyclic aromatic amines by human liver and colon. Carcinogenesis (Lond.), 12: 1839-1845, 1991.
10. 2 atoms of guanine. Chem. Res. Toxicol., 5: 479-490, 1992.
11. Minchin, R. F., Reeves, P. T., Teitel, C. H., McManus, M. E., Mojarrabi, B., Ilett, K. F., and Kadlubar, F. F. 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, 1992.
12. Chou, H-C., Lang, N. P., and Kadlubar, F. F. Metabolic activation of N-hydroxy arylamines and N-hydroxy heterocyclic amines by human sulfotransferase(s). Cancer Res., 55: 525-529, 1995.
13. 2-oxidized species of 2-amino-1-methyl-6-phenylimidazo(4,5-b]pyridine (PhIP) in rat liver. Carcinogenesis (Lond.), 12: 2239-2245, 1991.
14. Kaderlik, K., Mulder, G. J., Turesky, R. J., Lang, N. P., Teitel, C. H., Chiarelli, M. P., and Kadlubar, F. F. Glucuronidation of N-hydroxy heterocyclic amines by human and rat liver microsomes. Carcinogenesis (Lond.), 15: 1695-1701, 1994.
15. Kaderlik, K., Mulder, G. J., Shaddock, J. G., Casciano, D. A., Teitel, C. H., and Kadlubar, F. F. Effect of glutathione depletion and inhibition of glucuronidation and sulfation on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) metabolism, PhIP-DNA adduct formation and unscheduled DNA synthesis in primary rat hepatocytes. Carcinogenesis (Lond.), 15: 1711-1716, 1994.
16. Lin, D., Meyer, D. J., Ketterer, B., Lang, N. P., and Kadlubar, F. F. Effects of human and rat glutathione S-transferases on the covalent DNA binding of the N-acetoxy derivatives of heterocyclic amine carcinogens in vitro: a possible mechanism of organ specificity in their carcinogenesis. Cancer Res., 54: 4920-4926, 1994.
17. Gram, M. A., Hughes, N. C., Janezic, S. A., Goodfellow, G. H., Chen, H. J., Gaedigk, A., Yu, V. L., and Grewal, R. Human acetyltransferase polymorphisms. Mutat. Res., 376: 61-70, 1997.
18. Felton, J. S., Malfatti, M. A., Knize, M. G., Salmon, C. P., Hopmans, E. C., and Wu, R. W. Health risks of heterocyclic amines. Mutat. Res., 376: 37-41, 1997.
19. Kadlubar, F. F., Butler, M. A., Kaderlik, K. R., Chou, H-C., and Lang, N. P. Polymorphisms for aromatic amine metabolism in humans: relevance for human carcinogenesis. Environ. Health Perspect., 98: 69-74, 1992.
20. Badawi, A. F., Stern, S. J., Lang, N. P., and Kadlubar, F. F. Cytochrome P-450 and acetyltransferase expression as biomarkers of carcinogen-DNA adduct levels and human cancer susceptibility. Prog. Clin. Biol. Res., 395: 109-140, 1996.
21. Nebert, D. W., McKinnon R. A., and Puga A. Human drug-metabolizing enzyme polymorphisms: effects on risk of toxicity and cancer. DNA Cell Biol., 15: 273-280, 1996.
22. Lang, N. P., Butler, M. A., Massengill, J. P., Lawson, M., Stotts, R. C., Hauer-Jensen, M., and Kadlubar, F. F. Rapid metabolic phenotypes for acetyltransferase and cytochrome P4501A2 and putative exposure to food-borne heterocyclic amines increase the risk for colorectal cancer or polyps. Cancer Epidemiol. Biomark. Prev., 3: 675-682, 1994.
23. Miners, J. O., and Mackenzie, P. I. Drug glucuronidation in humans. Pharmacol. & Ther., 51: 347-369, 1991.
24. Lynch, A. M., Knize, M. G., Boobis, A. R., Gooderham, N. J., Davies, D. S., and Murray, S. Intra- and interindividual variability in systemic exposure in humans to 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and 2-amino-1-methyl- 6-phenylimidazo[4,5-b]pyridine, carcinogens present in cooked beef. Cancer Res., 52: 6216-6223, 1992.
25. Stillwell, W. G., Turesky, R. J., Gross, G A., Skipper, P. L., and Tannenbaum, S. R. Human urinary excretion of sulfamate and glucuronide conjugates of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). Cancer Epidemiol. Biomark. Prev., 3: 399-405, 1994.
26. Stillwell, W. G., Kidd, L. R., Wishnok, J. S., Tannenbaum, S. R., and Sinha, R. Urinary excretion of unmetabolized and Phase II conjugates of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in humans: relationship to cytochrome P4501A2 and N-acetyltransferase activity. Cancer Res., 57: 3457-3464, 1997.
27. Reistad, R., Rossland, O. J., Latva-Kala, K. J., Rasmussen, T., Vikse, R., Becher, G., and Alexander, J. Heterocyclic aromatic amines in human urine following a fried meat meal. Food Chem. Toxicol., 35: 945-955, 1997.
28. 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. CYPIA2-catalyzed conversion of dietary heterocyclic amines to their proximate carcinogens is their major route of metabolism in humans. Cancer Res., 54: 89-94, 1994.
29. Sinha, R., Rothman, N., Mark, S. D., Murray, S., Brown, E. D., Levander, O. A., Davies, D. S., Lang, N. P., Kadlubar, F. F., and Hoover, R. N. Lower levels of urinary 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in humans with higher CYPIA2 activity. Carcinogenesis (Lond.), 16: 2859-2861, 1995.
30. Turesky, R. J., Garner, R. C., Welti, D. H., Richoz, J., Leveson, S. H., Dingley, K. H., Turteltaub, K. W., and Fay, L. B. Metabolism of the food-borne mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in humans. Chem. Res. Toxicol., 11: 217-225, 1998.
31. Grivas, S. Synthesis of 3,8-dimethyl-2-nitro-3H-imidazo[4,5-f]quinoxaline, the 2-nitro analogue of the food carcinogen MeIQx. J. Chem. Res., (S): 84, 1988.
32. Turesky, R. J., Markovic, J., Bracco-Hammer, I., and Fay, L. B. 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 (MeIQx) in the rat. Carcinogenesis (Lond.), 12: 1847-1855, 1991.
33. Turesky, R. J., Bracco-Hammer, I., Markovic, J., Richli, U., Kappler, A., and Welti, D. H. 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, 1990.
34. 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. 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, 1994.
35. 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. Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites. Pharmacogenetics, 2: 116-127, 1992.
36. Turesky, R. J., Forster, C. M., Aeschbacher, H. U., Wurzner, H. P., Skipper, P. L., Trudel, L. J., and Tannenbaum, S. R. Purification of the food-borne carcinogens 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in heated meat products by immunoaffinity chromatography. Carcinogenesis (Lond.), 10: 151-156, 1989.
37. King, R. S., Casciano, D. A., and Kadlubar, F. F. NADH-dependent reduction of carcinogenic N-hydroxyarylamines by human and rat liver microsomes. Proc. Am. Assoc. Cancer Res., 39: 383, 1998.
38. Snyderwine, E. G., Welti, D. H., Davis, C. D., Fay, L. B., and Turesky, R. J. Metabolism of the food-derived carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in nonhuman primates. Carcinogenesis (Lond), 16: 1377-1384, 1995.
39. Ushiyama, H., Wakabayashi, K., Hirose, M., Itoh, H., Sugimura, T., and Nagao, M. Presence of carcinogenic heterocyclic amines in urine of healthy volunteers eating normal diet, but not of inpatients receiving parenteral alimentation. Carcinogenesis (Lond.), 12: 1417-1422, 1991.
40. Ji, H., Yu, M. C., Stillwell, W. G.. Skipper, P. L., Ross, R. K., Henderson, B. E., and Tannenbaum, S. R. Urinary excretion of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in white, black, and Asian men in Los Angeles County. Cancer Epidemiol. Biomark. Prev., 3: 407-411, 1994.
41. Kidd, L. R., Stillwell, W. G., Yu, M. C., Wishnok, J. S., Skipper, P. L., Ross, R. K., Henderson, B. E., and Tannenbaum, S. R. Urinary excretion of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in white, African-American, and Asian-American men in Los Angeles County. Cancer Epidemiol. Biomark. Prev., 8: 439-445, 1999.
42. DeMarini, D. M., Hastings, S. B., Brooks, L. R., Eischen, B. T., Bell, D. A., Watson, M. A., Felton, J. S., Sandler, R., and Kohlmeier, L. Pilot study of free and conjugated urinary mutagenicity during consumption of pan-fried meats: possible modulation by cruciferous vegetables, glutathione S-transferase-M1, and N-acelyltransferase-2. Mutat. Res., 381: 83-96, 1997.