Related Experiment Videos
Mouse specific-locus test for the induction of heritable gene mutations by dibromochloropropane (DBCP)
Abstract:
The nematocide DBCP (1,2-dibromo-3-chloropropane) produced negative results in a specific-locus test for gene-mutation induction in the germline of male (101 X C3H)F1 mice, most of which were treated with 5 daily intraperitoneal injections of 80 mg/kg (total exposure, 400 mg/kg); a few received lower exposures. For treated spermatogonial stem cells, the finding of 2 mutations among 39519 offspring--a rate almost identical to the control rate--rules out (at the 5% significance level) an induced mutation frequency greater than 2.0 times the historical control rate. From treated poststem-cell stages, no mutants were found among 6240 offspring, ruling out (at the 5% significance level) a multiple of 8.0 times the control for these cell types. A multiple rearrangement (7 chromosomes involved in 3 translocations) found in one of the mutants probably arose as a postmeiotic event not associated with the DBCP treatment. The fertility of DBCP-treated males was not disturbed, in keeping with the absence of germ-cell toxicity and dominant lethals found by other investigators in these mice, and in contrast to results in certain other species. While the treated (101 X C3H)F1 mice are Ah-responsive, other findings make it questionable whether biotransformation of DBCP to reactive intermediates is accomplished via the Ah-receptor system.
Insights
The nematocide DBCP (1,2-dibromo-3-chloropropane) did not induce gene mutations in male mouse germline cells. This study found no significant increase in mutation rates, suggesting DBCP is not a germline mutagen in mice.
Area of Science:
- Toxicology
- Genetics
- Reproductive Toxicology
Background:
- The nematocide DBCP (1,2-dibromo-3-chloropropane) is a chemical agent used for pest control.
- Previous studies have raised concerns about the potential mutagenicity of DBCP.
Purpose of the Study:
- To evaluate the potential of DBCP to induce gene mutations in the germline of male mice.
- To assess the genotoxic effects of DBCP on different stages of male germ cell development.
Main Methods:
- A specific-locus test was employed using (101 X C3H)F1 mice.
- Mice received daily intraperitoneal injections of DBCP at doses up to 80 mg/kg.
- Offspring were analyzed for induced mutations in treated spermatogonial stem cells and post-stem cell stages.
Main Results:
- No significant increase in mutation frequency was observed in treated spermatogonial stem cells compared to controls.
- No mutants were detected in offspring from treated post-stem cell stages.
- Male mouse fertility remained unaffected, and no dominant lethals were found.
Conclusions:
- DBCP does not appear to be a germline mutagen in male mice at the tested doses.
- The absence of germ cell toxicity and dominant lethals further supports a lack of genotoxic effect in male mice.
- The role of the Ah-receptor system in DBCP biotransformation remains questionable.