A deficiency for nucleotide excision repair strongly potentiates the mutagenic effectiveness of methyl bromide in Drosophila.
A DNA repair assay measuring hypermutability response in the absence of nucleotide excision repair (NER) was employed to study the impact of a deficiency in NER on the induction of forward mutations (X-chromosomal recessive lethals) by methyl bromide (MeBr) in Drosophila melanogaster. Postmeiotic male germ-cell stages reacted with MeBr were introduced in either NER competent oocytes (exr+) or in cells from the NER- strain mus-201. The high average M(exr-)/M(exr+) hypermutability ratio of 8.3 determined for MeBr is similar to the M(exr-)/M(exr+) indices found for other monofunctional alkylating agents with high Swain-Scott s values, such as methyl methanesulphonate and dimethyl sulphate. It is concluded that the genotoxic profile of methyl bromide is in keeping with those of high s-value alkylating agents but it seems incompatible with a methylating agent producing substantial amounts of O6 methylguanine.
Department of Radiation Genetics and Chemical Mutagenesis, Medical Genetics Centre South-West Netherlands-MGC, Sylvius Laboratories, Leiden.
L A
LA
Ballering
M J
MJ
Nivard
E W
EW
Vogel
D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics; D005260:Female; D005804:Genes, Lethal; D005808:Genes, Recessive; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D008297:Male; D009152:Mutagenicity Tests; D013094:Spermatozoa / Q000187:drug effects; D014960:X Chromosome
D000477:Alkylating Agents; D002273:Carcinogens; D006842:Hydrocarbons, Brominated; D006147:Guanine; C008449:O-(6)-methylguanine; C005218:methyl bromide