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.
D000818:Animals; D001711:Biotransformation; D004926:Escherichia coli / Q000235:genetics; D005821:Genetic Techniques; D008099:Liver / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D009153:Mutagens; D009242:N-Nitrosopyrrolidine / Q000378:metabolism / Q000494:pharmacology*; D009602:Nitrosamines / Q000494:pharmacology*; D051381:Rats
D009153:Mutagens; D009602:Nitrosamines; D009242:N-Nitrosopyrrolidine