Genetic effects of 1,3-butadiene on the mouse testis.

Abstract

1,3-Butadiene is a known male mouse germ-cell mutagen, to which humans may either be occupationally or environmentally exposed. Prolonged exposure to moderate or high doses in male mice can cause dominant lethal mutations and one report has indicated that 10 week inhalation administration of low doses can result in the production of malformed foetuses. The present study had dual purposes: (a) to attempt to clarify the suspected ability of sub-chronic (6 h/day, 5 days/wk, 10 weeks) low-dose exposure to 1,3-butadiene to induce heritable mutations in mouse male germ cells: (b) investigation of the relationships between testicular DNA damage, testicular DNA repair and foetal outcome. Adult male mice were exposed to low or moderate doses of 1,3-butadiene by inhalation sub-chronically or for a single 6 h period and either used for mating (sub-chronic exposure only) or for studies of DNA damage and repair. Litter size, dominant lethality and numbers of abnormal foetuses were determined the day preceding the normal day of parturition. Testicular DNA damage and repair were assessed by the Comet assay (for DNA damage) and the unscheduled DNA synthesis assay (for DNA repair). 1,3-Butadiene caused a statistically significant increase in dominant lethality at 125 ppm but not 12.5 ppm. No significant increase in DNA repair was found with either dose level or exposure period while only 6 h exposure to 125 ppm caused a small but significant increase in DNA damage as detected by the Comet assay. These effects demonstrate the reproductive genotoxicity of (125 ppm) 1,3-butadiene but do not confirm its ability to cause abnormalities in the offspring via the sperm. It is suggested that the relationship between 1,3-butadiene-induced DNA damage, DNA repair and heritable defects in the offspring may depend on the pattern of metabolites produced.