Differing activation pathways for 2-acetylaminofluorene to a mutagen in vitro.

Abstract The mutagenicity of 2-acetylaminofluorene (AAF) in S. typhimurium TA1538 was investigated using Ames' test and activation systems based upon rat- or cotton rat-liver post-mitochondrial supernatant (S9) fractions. Part of this study involved sub-fractionation of S9 into microsomes (M) and 100000 × gsupernatant (S100) fractions. With rat liver-derived fractions, most activity was associated with S100; M-activating potential was never greater than that achieved with S9. In cotton rats, most activating potential was associated with S9. This activity was greater than could be accounted for by the separated cotton-rat M and S100 components. Reconstituted, cross-species 'S9' fraction studies showed than that dominant determinant of S9 properties was the M fraction in both rats and cotton rats. The principal co-factor required in the activation reactions was NADPH, but it could be largely replaced by NADH. 7,8-Benzoflavone inhibited activation both in M and S100 whereas paraoxon had no effect upon rat S100 activation, but had a marked effect upon cotton-rat M activation.