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Induction of specific-locus and dominant lethal mutations in male mice in the low dose range by methyl
U H Ehling1, A Neuhäuser-Klaus
1GSF-Institut für Säugetiergenetik, Neuherberg, F.R.G.
Abstract:
Methyl methanesulfonate (MMS) induces specific-locus and dominant lethal mutations in spermatozoa and spermatids of mice. A dose of 15 mg/kg b.w. of MMS induces 9% dominant lethal mutations in the most sensitive germ-cell stages, corresponding to the mating intervals 5-8 and 9-12 days post treatment. A dose of 150 mg/kg b.w. of MMS in the same mating intervals induces 100% dominant lethal mutations. The sensitivity pattern for the induction of dominant lethal and specific-locus mutations is the same. In the mating interval 5-8 days a dose of 20 mg/kg b.w. of MMS induced 3.8 x 10(-5) mutations per locus per gamete. The yield of specific-locus and dominant lethal mutations in the low dose range increases proportionally with the dose. A dose given in 2, 4 or 5 fractions yields the same frequency of mutations as a single injection of the total dose. The additivity of small doses proves that the pre-mutational lesions are not or only partially repaired in these stages and that MMS is not or only partially detoxified. In addition, the frequency of dominant lethal and specific-locus mutations depends on the germ-cell stage.
Insights
Methyl methanesulfonate (MMS) causes genetic mutations in mouse sperm. Higher doses of MMS result in a 100% mutation rate, while lower doses show a proportional increase, indicating incomplete repair or detoxification.
Area of Science:
- Toxicology
- Genetics
- Reproductive Biology
Background:
- Methyl methanesulfonate (MMS) is a known mutagen.
- Understanding the genotoxic effects of MMS on male germ cells is crucial for assessing reproductive risks.
Purpose of the Study:
- To investigate the dose-response relationship of MMS-induced specific-locus and dominant lethal mutations in mouse spermatozoa and spermatids.
- To determine the sensitivity patterns of different germ cell stages to MMS mutagenesis.
Main Methods:
- Mice were treated with varying doses of MMS.
- Mutations were assessed using specific-locus and dominant lethal assays at different mating intervals post-treatment.
Main Results:
- MMS induces both specific-locus and dominant lethal mutations in a germ-cell stage-dependent manner.
- A dose of 150 mg/kg b.w. MMS resulted in 100% dominant lethal mutations in sensitive stages (5-12 days post-treatment).
- Low doses of MMS showed a proportional increase in mutation frequency, suggesting limited repair or detoxification.
Conclusions:
- The sensitivity to MMS-induced mutations is similar for both specific-locus and dominant lethal mutations.
- Fractionated doses of MMS yielded the same mutation frequency as single doses, indicating additivity of pre-mutational lesions.
- Germ cell stage significantly influences the frequency of MMS-induced mutations.