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

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.