PMID: 2494441Apr 1, 1989Paper

Dosage-response relationships for methyl methanesulfonate in Drosophila melanogaster spermatozoa: DNA methylation per nucleotide vs. sex-linked recessive lethal frequency

Mutation Research
W R LeeB J Byrne

Abstract

Two different mechanisms for mutagenesis following treatment with methyl methanesulfonate (MMS) are suggested from the dose-response curve that is best fit by the linear quadratic model where m = 0.130D + 0.038D2 (D = dose measured as alkylations per nucleotide X 10(3), APdN; m = percent sex-linked recessive lethals, SLRL). A predominant component of the dose-response curve at moderate to high dose is the quadratic component which is interpreted as the result of two single-strand breaks. The distribution of methyl adducts in vivo is consistent with the previously determined in vitro distribution of methyl adducts on DNA following treatment with MMS. With the use of HPLC, 82% of the 3H-labeled adducts are found on the N-7 of guanine. It has previously been shown by both in vitro studies and in vivo correlation with mutagenesis that the N-7 alkyl guanine is not itself a predominately genotoxic lesion; however, N-7 alkyl guanine destabilizes guanine resulting in an increased rate of hydrolysis producing apurinic sites. In data presented in this paper, the loss of labeled adducts is shown to be at a rate consistent with hydrolysis of the destabilized alkyl guanine. The apurinic site thus produced should be converted to single-stran...Continue Reading

References

Nov 1, 1976·Mutation Research·F J De Serres
Jan 1, 1973·Annual Review of Genetics·C D Laird
May 1, 1970·Mutation Research·M A Kastenbaum, K O Bowman

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Citations

Aug 1, 1995·Mutation Research·E W Vogel, A T Natarajan
Jan 1, 1989·Environmental and Molecular Mutagenesis·W R Lee
Jan 1, 1993·Environmental and Molecular Mutagenesis·K S TaoJ A Heddle

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