Preferential formation of deletions following in vivo exposure of postmeiotic Drosophila germ cells to the DNA etheno-adduct-forming carcinogen vinyl carbamate

Environ Mol Mutagen. 1997;30(3):321-9. doi: 10.1002/(sici)1098-2280(1997)30:3<321::aid-em11>3.0.co;2-f.

Abstract

DNA sequence changes induced in the vermilion gene of Drosophila following in vivo treatment of postmeiotic male germ cells with vinyl carbamate (VCA), an etheno-adduct-forming carcinogen, are primarily deletions. With VCA, 65% (13/20) of the vermilion mutants isolated from crosses of NER+ (nucleotide excision repair) males with NER+ females and 40% (6/15) obtained from matings with NER- females were intra- or multi-locus deletions. Due to the insufficiently low mutagenic activity in NER+ genotypes of vinyl bromide (VB), another epsilon-adduct-forming carcinogen, vermilion mutants could only be isolated from crosses of VB-treated males with NER- females. Of 14 vermilion mutants induced by VB, three carried large deletions. Twenty-two of 23 base substitutions derived from either VCA or VB experiments fell into one of the four categories expected from epsilon-adducts: three vermilion mutants had GC-->AT transitions, five had AT-->GC transitions, 7 carried GC-->TA transversions, and 7 were AT-->TA transversions. In view of the similarities in the response of mouse and Drosophila germ lines to several classes of alkylating agents, a high incidence of deletions is predicted to occur as well in postmeiotic germ cells of mice exposed to these types of agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogens / pharmacology*
  • Drosophila / genetics*
  • Female
  • Follow-Up Studies
  • Gene Deletion*
  • Genetic Markers
  • Germ Cells / drug effects*
  • Male
  • Mutagens / pharmacology*
  • Urethane / analogs & derivatives*
  • Urethane / pharmacology
  • Vinyl Chloride / pharmacology

Substances

  • Carcinogens
  • Genetic Markers
  • Mutagens
  • Urethane
  • vinyl carbamate
  • Vinyl Chloride