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Genetics, Vol 131, 673-682, Copyright © 1992
INVESTIGATIONS |
Molecular Analysis of Mutations Induced in the vermilion Gene of Drosophila melanogaster by Methyl Methanesulfonate
MJM. Nivard, A. Pastink and E. W. Vogel
MGC-Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden, Sylvius Laboratories, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands
The nature of DNA sequence changes induced by methyl methanesulfonate (MMS) at the vermilion locus of Drosophila melanogaster was determined after exposure of postmeiotic male germ cell stages. MMS is a carcinogen with strong preference for base nitrogen alkylation (s = 0.86). The spectrum of 40 intralocus mutations was dominated by AT -> GC transitions (23%), AT -> TA transversions (54%) and deletions (14%). The small deletions were preferentially found among mutants isolated in the F(1) (8/18), whereas the AT -> GC transitions exclusively occurred in the F(2) (6/22). The MMS-induced transversions and deletions are presumably caused by N-methyl DNA adducts, which may release apurinic intermediates, known to be a time-related process. Furthermore, MMS produces multilocus deletions, i.e., at least 30% of the F(1) mutants analyzed were of this type. A comparison of the mutational spectra of MMS with that produced by ethylnitrosourea (ENU), also in the vermilion locus of Drosophila, reveals major differences: predominantly transition mutations (61% GC -> AT and 18% AT -> GC) were found in both the F(1) and F(2) spectrum induced by ENU. It is concluded that the mutational spectrum of MMS is dominated by nitrogen DNA adducts, whereas with ENU DNA sequence changes mainly arose from modified oxygen in DNA.
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