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Induction of specific-locus mutations in male mice by ethyl methanesulfonate (EMS)
U H Ehling1, A Neuhäuser-Klaus
1GSF-Institut für Säugetiergenetik, Neuherberg, F.R.G.
Abstract:
Using a sequential mating procedure, the induction of specific-locus mutations by ethyl methanesulfonate (EMS) was reinvestigated in male mice. Doses of 175 mg/kg b.w. and 250 mg/kg b.w. of EMS induce gene mutations in the mating intervals 5-8 and 9-12 days post treatment. However, only the frequency of dominant lethal mutations increases with the dose, not the frequency of specific-locus mutations. This observation implies that with a higher dose of EMS a larger fraction of mutagenized spermatozoa and spermatids are selectively eliminated, leading to underestimation of the specific-locus mutation yield at high doses. EMS does not induce specific-locus mutations in spermatogonia.
Insights
Ethyl methanesulfonate (EMS) induces gene mutations in mice, but higher doses may underestimate mutation rates due to selective elimination of damaged sperm. EMS did not induce mutations in spermatogonia.
Area of Science:
- Genetics
- Toxicology
- Reproductive Biology
Background:
- Ethyl methanesulfonate (EMS) is a known mutagen used to study genetic damage.
- Understanding dose-response relationships for mutagens is crucial for risk assessment.
- Previous studies have investigated EMS-induced mutations in male mice.
Purpose of the Study:
- To re-evaluate the induction of specific-locus mutations by EMS in male mice using a sequential mating procedure.
- To determine the effect of different EMS doses on mutation frequencies at specific loci and dominant lethal mutations.
- To investigate the impact of EMS on different stages of spermatogenesis.
Main Methods:
- Sequential mating procedure in male mice.
- Administration of ethyl methanesulfonate (EMS) at doses of 175 mg/kg and 250 mg/kg body weight.
- Analysis of specific-locus mutations and dominant lethal mutations at different mating intervals post-treatment.
Main Results:
- EMS induced gene mutations in mating intervals 5-8 and 9-12 days post-treatment at both tested doses.
- The frequency of dominant lethal mutations increased with EMS dose.
- The frequency of specific-locus mutations did not increase with the higher EMS dose, suggesting selective elimination of mutagenized germ cells.
- EMS did not induce specific-locus mutations in spermatogonia.
Conclusions:
- Higher doses of EMS may lead to an underestimation of specific-locus mutation yields due to selective elimination of mutagenized spermatozoa and spermatids.
- EMS does not appear to induce specific-locus mutations in spermatogonia under the conditions tested.
- The findings highlight the complexity of dose-response relationships for chemical mutagens in mammalian germ cells.