Evidence of partial involvement of P-450 2D in mutagenic activation of benzo(a)pyrene in liver S-9 fraction from untreated rats.

Abstract

In order to clarify which species of cytochrome P-450 is involved in activation of benzo(a)pyrene (BP) in untreated rat liver, strain and sex differences in the ability of rat liver 9000 g supernatant (S-9) to mutagenically activate BP was investigated using Ames test. The numbers of histidine revertants in Ames test after pre-incubation of TA 98 strain of Salmonella typhimurium and BP with liver S-9 from male rats were markedly higher than those obtained using female rats. In addition, a marked strain difference (Wistar > DA) in the ability of liver S-9 from Wistar and DA rats to activate BP was observed. Antibody against cytochrome P-450 2D inhibited up to 50% of the revertant formation by the activation of BP with liver S-9 from male Wistar rats. These results indicate the partial involvement of cytochrome P-450 2D subfamily as well as cytochrome P-450 species specific to male rats in activation of BP to ultimate mutagen in untreated rat liver.