The mutagenicity of nitrosopyrrolidine is related to its metabolism

Various cell fractions from rat liver were tested for their ability to convert nitrosopyrrolidine (NO-PYR) to products which were mutagenic to E. coli in liquid-incubation assays. Microsomes alone produced only a small number of tyr+ revertants, approximately 40/10(8) survivors), while the S100 supernatant produced none at all. However, the S8 Fraction or combinations of microsomes and the S100 supernatant, yielded 300-400 tyr+ revertants/10(8) survivors. Neither products of the microsomal, nor microsome + supernatant reactions were mutagenic in the absence or presence of cellular fractions. These results suggest that bacterial mutagens are formed during the microsomal metabolism of NO-PYR to 2-hydroxytetrahydrofuran by alpha-hydroxylation, but not during the metabolism of 2-hydroxytetrahydrofuran by the S100 supernatant enzymes. Possible roles of the supernatant enzymes in the formation of mutagenic intermediates during the initial alpha-hydroxylation of NO-PYR are discussed.