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[Mutagenic effect of chemical compounds on laboratory mice]
Abstract:
Mutagenic effect of thioTEPA applied at a dose of 1.25 mg/kg was studied in late spermatids of C57BL/L male mice. The mutagen induced dominant lethal mutations in germ cells (39%) and symmetric translocations in 33.5% of F1 male offspring. The common frequency of sperms with chromosome mutations was 60%, that is ten times as much as the mutagenic effect in bone marrow cells. 39% of embryos at 3.5 days of development died or delayed their development at 2--22 blastomers stages. Structure chromosome aberrations were found in the cells of such embryos. The scheme of genetical screening of chemical compounds in laboratory mice, based on the data obtained early and in the present experiment, is proposed.
Insights
The mutagen thioTEPA caused significant genetic damage in male mice, including dominant lethal mutations and chromosome translocations. This highlights its potent mutagenic effects on germ cells and early embryos.
Area of Science:
- Reproductive toxicology
- Genetics
- Developmental biology
Context:
- Investigating the genotoxicity of chemical compounds is crucial for risk assessment.
- ThioTEPA is a known alkylating agent with potential mutagenic properties.
- Late spermatids represent a sensitive stage for evaluating mutagen-induced germ cell damage.
Purpose:
- To assess the mutagenic effect of thioTEPA in male mouse germ cells.
- To quantify the incidence of dominant lethal mutations and chromosome aberrations.
- To evaluate the impact on early embryonic development and propose a screening scheme.
Summary:
- ThioTEPA at 1.25 mg/kg induced dominant lethal mutations (39%) and symmetric translocations (33.5%) in male mice.
- Sperm with chromosome mutations reached 60%, significantly higher than in bone marrow cells.
- Embryonic development was impaired, with 39% of embryos showing developmental delays or death and structural chromosome aberrations.
Impact:
- The study reveals thioTEPA's potent mutagenicity in male germ cells and its transgenerational effects.
- Findings contribute to understanding chemical-induced reproductive toxicity.
- A proposed scheme for genetical screening of chemical compounds in mice is presented.