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Rhesus monkey (Macaca mulatta) model in genetic toxicology mitomycin C clastogenicity in germ cells
Abstract:
The value of rhesus monkeys (Macaca mulatta) as a genetic toxicology model is limited by their scarcity, expense, and impracticality of progeny testing. However, in some special circumstances, e.g., accidental exposure of humans to potential mutagens, rhesus monkeys or other primates may provide a superior animal model to help to cope with a difficult public health situation. Using the testis as a target organ we found that when primary spermatocytes were treated in pre-leptotene stage with 1 mg mitomycin C/kg body weight, the frequency of exchanges, fragments, sex-chromosome and autosomal univalents increased significantly at diakinesis-metaphase I. This response was absent in cells treated during diplotene, late pachytene or during spermatogonial stages. We suggested that animals should be evaluated not only for genetic toxicology parameters, but also toxicologically, histologically, behaviorally, for carcinogenesis and seminal cytology. Whenever possible, the animals should be recycled.
Insights
Rhesus monkeys show increased genetic damage in sperm cells after exposure to mitomycin C during specific developmental stages. This highlights their potential as a primate model for mutagenicity testing in critical public health scenarios.
Area of Science:
- Primate toxicology
- Genetic toxicology
- Reproductive toxicology
Background:
- Rhesus monkeys (Macaca mulatta) are valuable but limited models for genetic toxicology due to cost and scarcity.
- Primates may serve as superior models in specific public health situations, such as accidental human exposure to mutagens.
Purpose of the Study:
- To evaluate the rhesus monkey as a genetic toxicology model, specifically investigating the effects of mitomycin C on spermatocyte development.
- To determine the sensitivity of different spermatocyte stages to mutagenic insult.
Main Methods:
- Rhesus monkey testes were used as the target organ.
- Primary spermatocytes were treated with mitomycin C (1 mg/kg) at the pre-leptotene stage.
- Chromosomal aberrations (exchanges, fragments, univalents) were analyzed at diakinesis-metaphase I.
Main Results:
- Mitomycin C treatment at the pre-leptotene stage significantly increased chromosomal exchanges, fragments, and univalents in diakinesis-metaphase I cells.
- No significant response was observed when cells were treated during diplotene, late pachytene, or spermatogonial stages.
Conclusions:
- The pre-leptotene spermatocyte stage in rhesus monkeys is sensitive to mitomycin C-induced genetic damage.
- Comprehensive toxicological evaluation, including genetic, histological, and seminal cytology assessments, is recommended for primate models.
- Recycling of animals, where feasible, is suggested to maximize the utility of these models.