The mutagenicity and DNA base sequence changes induced by 1-nitroso- and 1-nitropyrene in the cI gene of lambda prophage.
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.
Stanton
C A
CA
Cancer Research Unit, University of York, Heslington, UK.
Garner
R C
RC
Martin
C N
CN
D010582:Bacteriophage lambda / Q000235:genetics; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004926:Escherichia coli / Q000235:genetics; D005814:Genes, Viral; D008969:Molecular Sequence Data; D009154:Mutation / Q000187:drug effects*; D011721:Pyrenes
D011721:Pyrenes; C044707:1-nitrosopyrene; C032668:1-nitropyrene