An important role for cytosol in the microsomal metabolism of N-nitrosodimethylamine to a mutagen: evidence for two different mutagenic metabolites.
Microsomal-mediated mutagenesis induced by N-nitrosodimethylamine (NDMA) in Salmonella TA100 at neutral pH was only slightly affected by cytosol and was similar in its threshold type dose-response curve to mutagenesis induced by direct-acting N-nitroso-N-methyl compounds. However, mutagenesis in strain TA104 was greatly enhanced by cytosol and this mutagenesis did not exhibit a threshold. In the presence of microsomes alone NDMA was more potent in TA100 than TA104, but in the presence of microsomes plus cytosol (S-9 fraction) this order was reversed at the doses tested. A possible explanation for these results is that NDMA is metabolized by microsomes to a mutagen (presumably methyldiazonium ion; MDI) that is more potent in TA100 than in TA104, but in the presence of S-9 fraction a fraction of the NDMA is metabolized by a pathway leading to a different mutagen with a different specificity. The ratio of metabolism via these pathways appears to be dependent on pH.
Guttenplan
J B
JB
Department of Biochemistry, New York University Dental Center, NY.
D000818:Animals; D006224:Cricetinae; D003600:Cytosol / Q000502:physiology*; D004128:Dimethylnitrosamine / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000378:metabolism*; D009153:Mutagens / Q000378:metabolism*; D012475:Salmonella / Q000378:metabolism
D009153:Mutagens; D004128:Dimethylnitrosamine