Metabolism of aflatoxin B1, benzo[a]pyrene, and 1,2-dimethylhydrazine by cultured rat and human colon.
A model system for comparing carcinogen metabolism between human and rat colon has been developed. Tissue explants maintained under chemically defined conditions were treated with radioactively labeled carcinogens. After incubation for 24 hours, the binding of radioactive carcinogen to DNA was quantitated. Further, the carcinogen-DNA adducts and carcinogen metabolites released into the culture media were identified. Both human and rat colon activate benzo[a]pyrene (BP), aflatoxin B1 (AFB), and 1,2-dimethylhydrazine (DMH) into chemical species that reacted with cellular macromolecules. When human and rat colons were compared, the metabolism of AFB and DMH was qualitatively similar - the same major carcinogen-DNA adducts and metabolic profile. However, the mean binding levels of DMH and AFB to colonic DNA were higher in rats than in humans. BP-guanine adducts were the major adducts formed by both rat and human colonic DNA. However, BP-adenine adducts were observed in rat colonic DNA but not in human colonic DNA. A positive correlation for the binding of BP and DMH to human DNA of different individuals was observed, but no correlation was found between BP and AFB. The data suggest that similar enzyme systems may be involved in the metabolism of BP and DMH, whereas different enzymes might be involved in the metabolic activation of AFB.
Autrup, H; Schwartz, RD; Essigmann, JM; Smith, L; Trump, BF; Harris, CC
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