PMID: 2114533Jul 1, 1990Paper

Comparison of dose-response relationships for ethyl methanesulfonate and 1-ethyl-1-nitrosourea in Drosophila melanogaster spermatozoa

Mutation Research
W R LeeA B Tucker

Abstract

The relative importance of different sites of alkylation on DNA was determined by comparing two ethylating agents. 1-Ethyl-1-nitrosourea (ENU) ethylates DNA with a higher proportion of total adducts on ring oxygens than ethyl methanesulfonate, which ethylates with a higher proportion of total adducts on the N-7 of guanine. Research with somatic cells in culture and prokaryotes strongly suggests that O6-guanine (O6-G) is the principal genotoxic site. To determine the importance in germ-line mutagenesis of the O6-G site relative to the N-7 of guanine, dose-response curves were constructed for both ENU and EMS, where dose was measured as total adducts per deoxynucleotide (APdN) and response as sex-linked recessive lethals (SLRL) induced in Drosophila melanogaster spermatozoa. For both mutagens the dose response curve was linear and extrapolated to the origin. The dose-response curve for ENU was fit to an equation m = 6.2D, and the dose response curve for EMS, from this and previous experiments, was m = 3.2D where m = %SLRL and D = APdN X 10(-3). Therefore, ENU is 1.9 times more efficient per adduct in inducing SLRL mutations than EMS. In vitro studies showed that ENU induced 9.5% of its total adducts on O6-G while EMS induced 2.0%...Continue Reading

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Citations

Aug 1, 1995·Mutation Research·E W Vogel, A T Natarajan
Feb 13, 2003·Mutation Research·Nataliya SavinaTatyana Kuzhir
Jun 26, 2001·Environmental and Molecular Mutagenesis·W R LeeV L Wilson
Mar 16, 2018·G3 : Genes - Genomes - Genetics·Kristie WrasmanBeverly Wendland
Jun 27, 2001·Nature Neuroscience·S Yamamoto, S Kitazawa

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