The role of metabolism of chemicals with respect to carcinogenicity tests.
Precarcinogens can be activated to carcinogenic effective compounds--ultimate carcinogens--by mammalian enzymes in vivo. In in vitro short-term tests, estimating effects which correlate with carcinogenicity in vivo of a chemical, these enzymes are represented by liver postmitochondrial fractions (S9) added to the test system. For the characterization and standardization of these S9 preparations we estimated certain enzymes involved in activating process: benzo(a)pyrene hydroxylase, the N-demethylases of dimethylnitrosamine, 4-dimethylaminoazobenzene and for a comparison, ethylmorphine as well as the azoreductase with 4-dimethylaminoazobenzene as a substrate. In order to get preparations with high enzyme activities, the animals such as rats, mice, hamsters and rabbits were pretreated by inducers such as polychlorinated biphenyls, phenobarbital, and 3-methylcholanthrene. We have observed species-specific differences in basic enzymatic patterns and in the degree of enzyme activities after induction. So it is principally possible to find out, whether or not a distinct animal species or strain is capable of metabolizing certain precarcinogens. Our aim is to optimize the evaluation of the carcinogenic risk of chemicals to humans by including human enzyme preparation in short-term tests.
D015073:2-Acetylaminofluorene / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D002415:Cats; D006224:Cricetinae; D004128:Dimethylnitrosamine / Q000378:metabolism; D004285:Dogs; D004790:Enzyme Induction; D000882:Haplorhini; D006801:Humans; D008099:Liver / Q000201:enzymology; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D010634:Phenobarbital / Q000494:pharmacology; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D013045:Species Specificity
D002273:Carcinogens; D008748:Methylcholanthrene; D015073:2-Acetylaminofluorene; D011078:Polychlorinated Biphenyls; D001189:Aryl Hydrocarbon Hydroxylases; D004128:Dimethylnitrosamine; D010634:Phenobarbital