Cytosolic potentiation of the rat hepatic microsome mediated mutagenicity of benzidine.
The role of the cytosolic fraction in the S9-mediated metabolic activation of benzidine to mutagens in the Ames test was investigated using hamster and rat hepatic preparations. Rat microsomes alone were poor activators of benzidine compared to hamster microsomes, at least partly explaining the well known superiority of S9 preparations from the latter species in activating this amine. Supplementation of rat microsomal preparations with the cytosolic fraction from hamsters and to a lesser extent from rats enhanced the bioactivation of benzidine. When hamster microsomal preparations were supplemented with rat or hamster cytosolic fractions no significant effect was observed. Cytosolic fractions from either species could not activate benzidine to mutagens in the absence of microsomes. The cytosolic potentiation of the microsome-mediated activation of the amine was not inducible by Aroclor 1254. Similarly, the microsome-mediated activation of benzidine was not enhanced by Aroclor 1254 pre-treatment of the rats, when mutagenicity is expressed per nmol of cytochrome P-450. It is concluded that (i) the cytosolic fraction may play an important role in the metabolic activation by S9 preparations of chemical carcinogens such as benzidine, and (ii) the Aroclor-induced isozymes of cytochrome P-450 do not catalyse the N-hydroxylation of benzidine.
Smith
J N
JN
Department of Biochemistry, University of Surrey, Guildford, UK.
Ioannides
C
C
D000818:Animals; D001560:Benzidines / Q000378:metabolism / Q000494:pharmacology*; D001711:Biotransformation; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D009154:Mutation; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects
D001560:Benzidines; D009153:Mutagens; C029876:benzidine; D006899:Mixed Function Oxygenases