The mutagenicity and DNA base sequence changes induced by 1-nitroso- and 1-nitropyrene in the cI gene of lambda...

The mutagenicity of 1-nitropyrene and its reduced metabolite 1-nitrosopyrene was determined in the lambda cI gene of an Escherichia coli uvr- lysogen. 1-Nitropyrene induced a mutation frequency of 3.8 x 10(-6), which was approximately 2-fold higher than the background mutation frequency, whereas an equimolar dose of 1-nitrosopyrene induced a much higher mutation frequency of 1.4 x 10(-4). Previous studies have established that both compounds form the same premutagenic lesion, viz. N-(deoxyguanosin-8-yl)-1-aminopyrene in bacterial DNA. In order to determine how this initial premutational lesion is converted to a stable heritable mutation, DNA sequences were determined for 30 mutations induced by 1-nitrosopyrene that mapped between bp 1 and 352 in the lambda cI gene of E.coli lysogens. We show here that these mutations are mainly frameshifts involving the addition or deletion of a single GC or CG base pair. A small proportion of mutations were base substitutions which were equally divided between transitions and transversions. These also occurred primarily at GC or CG sites.