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

The mutagenicity of 1-nitropyrene and its reduced metabolite1-nitrosopyrene was determined in the lambda cI gene of an Escherichiacoli uvr^- lysogen. 1-Nitropyrene induced a mutation frequencyof 3.8 x 10^–6, which was {small tilde} 2-fold higher thanthe background mutation frequency, whereas an equimolar doseof 1-nitrosopyrene induced a much higher mutation frequencyof 1.4 x 10^–4. Previous studies have established thatboth compounds form the same premutagenic lesion, viz. N-(deoxyguanosin-8-yl)-l-aminopyrenein bacterial DNA. In order to determine how this initial premutationallesion is converted to a stable heritable mutation, DNA sequenceswere determined for 30 mutations induced by 1-nitrosopyrenethat mapped between bp 1 and 352 in the lambda cI gene of E.colilysogens. We show here that these mutations are mainly frameshiftsinvolving the addition or deletion of a single GC or CG basepair. A small proportion of mutations were base substitutionswhich were equally divided between transitions and transversions.These also occurred primarily at GC or CG sites.