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Induction of specific-locus and dominant lethal mutations in male mice by busulfan
U H Ehling1, A Neuhäuser-Klaus
1GSF-Institut für Säugetiergenetik, Neuherberg, F.R.G.
Abstract:
The chemotherapeutic agent busulfan was tested for the induction of dominant lethal and specific-locus mutations in male mice. A dose of 5 mg/kg b.w. of busulfan induces dominant lethal mutations in spermatozoa. A dose of 20 mg/kg b.w. induces dominant lethal mutations in spermatozoa and spermatids. A total of 83,196 offspring were scored in the specific-locus experiments. Busulfan-induced specific-locus mutations were recovered in spermatozoa and spermatids, but not in spermatogonia. The sensitivity patterns for the induction of dominant lethal and specific-locus mutations by busulfan in germ cells of male mice are similar but not identical.
Insights
Busulfan, a chemotherapy drug, causes genetic mutations in male mice. It induces dominant lethal and specific-locus mutations in sperm cells (spermatozoa and spermatids) but not in spermatogonia.
Area of Science:
- Toxicology
- Genetics
- Reproductive Biology
Background:
- Busulfan is a chemotherapeutic agent used in cancer treatment.
- Understanding its genotoxic effects is crucial for assessing risks in patients.
Purpose of the Study:
- To investigate the mutagenic potential of busulfan in male mice.
- To determine the specific germ cell stages affected by busulfan-induced mutations.
Main Methods:
- Male mice were administered varying doses of busulfan (5 mg/kg and 20 mg/kg).
- Dominant lethal mutations were assessed by examining offspring viability.
- Specific-locus mutations were evaluated by scoring 83,196 offspring.
Main Results:
- Busulfan induced dominant lethal mutations in spermatozoa at 5 mg/kg.
- At 20 mg/kg, busulfan induced dominant lethal mutations in spermatozoa and spermatids.
- Specific-locus mutations were observed in spermatozoa and spermatids, but not in spermatogonia.
Conclusions:
- Busulfan is a mutagen in male mouse germ cells.
- The sensitivity of germ cell stages to busulfan-induced mutations is similar for dominant lethal and specific-locus mutations but not identical.