In vivo and in vitro effects of 3-methylcholanthrene on the microsome-mediated in vitro mutagenicity of 2-acetylaminofluorene.
Pretreatment of rat, hamster or mouse by 3-methylcholanthrene (3-MC) largely induces the liver microsomal N-hydroxylase activity. The same pretreatment given simultaneously with 2-acetylaminofluorene (2-AAF) inhibits the hepatocarcinogenicity in the rat but not in the hamster. The present report compared the in vivo and in vitro effects of 3-MC on liver microsomal N-hydroxylation and liver microsome-mediated mutagenicity of 2-AAF in hamster, rat and mouse. The induction of hamster or mouse liver microsomal N-hydroxylase activity correlated well with the increase in the microsome-mediated mutagenicity of 2-AAF. With rat, however, even though the N-hydroxylase activity is largely enhanced, microsome-mediated mutagenicity is significantly reduced after pretreatment with 3-MC. Such a reduction parallels a decrease in enzyme affinity. Added in vitro to the incubation medium, 3-MC (microM concentration) inhibits both the N-hydroxylase activity and the microsome-mediated mutagenicity of 2-AAF. Those data are discussed in relationship with the biological interactions between 3-MC and 2-AAF.
D015073:2-Acetylaminofluorene / Q000494:pharmacology*; D000818:Animals; D006224:Cricetinae; D004347:Drug Interactions; D066298:In Vitro Techniques; D008748:Methylcholanthrene / Q000494:pharmacology*; D051379:Mice; D008862:Microsomes, Liver / Q000502:physiology*; D006899:Mixed Function Oxygenases / Q000494:pharmacology; D009153:Mutagens; D051381:Rats; D012486:Salmonella typhimurium / Q000235:genetics; D013045:Species Specificity
D009153:Mutagens; D008748:Methylcholanthrene; D015073:2-Acetylaminofluorene; D006899:Mixed Function Oxygenases; C030541:arylamide N-hydroxylase