Competitive inhibitory effect of microsomal N-hydroxylase, a possible explanation for the in vivo in inhibition of 2-acetylaminofluorene carcinogenicity by 3-methylcholanthrene.
The kinetic properties of the N-hydroxylation of 2-acetylaminofluorene (2-AAF) are studied with microsomal preparations of livers from both control and 3-methylcholanthrene (3-MC)-pretreated rats and hamsters. The level of basal enzymatic activity is higher in hamster than in rat liver; 3-MC induces the activity in both animals. When added in vitro to incubation mixture, 3-MC competitively inhibits the N-hydroxylase activity. When fed to rats simultaneously with 2-AAF, 3-MC suppresses the carcinogenicity of the acetylated arylamine by inhibiting the first step in its activation pathway. Hamster tissues are not protected by this pretreatment because the level of N-hydroxylase activity is too high.
D015073:2-Acetylaminofluorene / Q000037:antagonists & inhibitors*; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D006224:Cricetinae; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000032:analysis* / Q000037:antagonists & inhibitors; D051381:Rats; D013045:Species Specificity
D002273:Carcinogens; D008748:Methylcholanthrene; D015073:2-Acetylaminofluorene; D006899:Mixed Function Oxygenases