EFFECTS OF CYTOSOL ON MUTAGENESIS INDUCED BY N-NITROSODIMETHYLAMINE, N-NITROSOMETHYLUREA AND ALPHA-ACETOXY-N-NITROSODIMETHYLAMINE IN DIFFERENT STRAINS OF SALMONELLA - EVIDENCE FOR DIFFERENT ULTIMATE MUTAGENS FROM N-NITROSODIMETHYLMINE

N-Nitrosodimethylamine (NDMA), but not N-nitroso-N-methylurea (MNU) wa s more mutagenic in the Salmonella hisG428 strain, TA104, than in the hisG46 strain, TA100 in the presence of rat or hamster liver S-9 mix. As both NDMA and MNU can give rise to methyldiazonium ion (MDI) it app ears that NDMA can be metabolized to an additional mutagen with a high er activity in TA104. The effects of UV and error-prone repair on NDMA and MNU-induced mutagenesis in TA104 were also different. Alpha-Aceto xy-NDMA, which gives rise to the NDMA metabolite, alpha-hydroxy-NDMA, was more mutagenic in TA104 than TA100, under certain conditions. Seve ral metabolites of NDMA (formaldehyde, 1,1-dimethylhydrazine and nitri te) were not significantly mutagenic at the concentrations that could have been generated from NDMA. It was previously reported that the mic rosomal-mediated mutagenesis induced by NDMA is greatly increased by c ytosol in TA104, but not in TA100, The current study found that when c ytosol was separated into a high and a low mol. wt fraction, neither g reatly enhanced microsomal-mediated mutagenesis by NDMA in TA104. Addi tion of NAD to the high, but not the low mol. wt fraction resulted in greatly enhanced activation of NDMA to a mutagen in TA104. The enhance ment by cytosol of NDMA-induced mutagenesis in hisG428 was only observ ed when both microsomes and cytosol were simultaneously present. These observations indicate that (i) the precursor to the ultimate mutagen is relatively short-lived; and (ii) the metabolism of a-hydroxy-NDMA t o a secondary mutagenic metabolite, possibly N-nitroso-N-methylformami de, by alcohol dehydrogenase may be responsible for the ultimate mutag en with relatively high activity in TA104.