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Inhibition of genotoxic effects of mammalian germ cell mutagens
M D Waters1, H F Stack, M A Jackson
1U.S. Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC, USA.
Abstract:
Germ cell mutagens are among the most important chemicals for which chemopreventive agents should be sought and mechanistically defined. These mutagens may include environmental chemicals as well as drugs. In this investigation, the literature was reviewed for substances antimutagenic (or anticlastogenic) to compounds identified as mutagens in at least two germ cell studies. A complete matrix of test results was prepared to identify commonly tested pairs of germ cell mutagens and antimutagens. The categories of antimutagens most tested included vitamins, fatty acids, thiols, tannins and other phenolics. The most frequently studied mutagens were benzo[a]pyrene, cyclophosphamide, mitomycin C, and bleomycin. Based on the availability of the most relevant data, the analysis presented here focused on in vivo tests, specifically on bone marrow cytogenetics. The results indicated that antimutagens commonly found in the diet or endogenously in the body effectively antagonized the cytogenetic damage induced in the bone marrow by most of the germ cell mutagens studied to date. Bone marrow micronucleus and chromosomal aberration assays, which detect systemically active mutagens, may be predictive of similar mitigating effects in germ cells. Test results from antimutagenicity studies in germ cells, though limited, were comparable to the results from studies in the mouse bone marrow micronucleus test.
Insights
Dietary and endogenous antimutagens effectively counteract germ cell mutagen damage. Bone marrow tests may predict antimutagenic effects in germ cells, aiding chemoprevention research.
Area of Science:
- Toxicology
- Genetics
- Chemoprevention
Background:
- Germ cell mutagens pose significant risks, necessitating the identification of chemopreventive agents.
- Environmental chemicals and drugs can act as germ cell mutagens.
- Antimutagenic substances are crucial for mitigating mutagen-induced damage.
Purpose of the Study:
- To review literature for substances with antimutagenic (or anticlastogenic) effects against identified germ cell mutagens.
- To analyze test results and identify commonly studied mutagen-antimutagen pairs.
- To focus on in vivo bone marrow cytogenetics data for analysis.
Main Methods:
- Literature review of antimutagenicity studies.
- Matrix preparation of test results for germ cell mutagens and antimutagens.
- Focus on in vivo bone marrow cytogenetic assays (micronucleus and chromosomal aberration).
Main Results:
- Vitamins, fatty acids, thiols, tannins, and phenolics were frequently tested antimutagens.
- Benzo[a]pyrene, cyclophosphamide, mitomycin C, and bleomycin were frequently studied mutagens.
- Endogenous and dietary antimutagens effectively reduced bone marrow cytogenetic damage from germ cell mutagens.
Conclusions:
- Dietary and endogenous antimutagens show promise in protecting against germ cell mutagen-induced damage.
- Bone marrow assays may serve as predictive models for germ cell antimutagenicity.
- Further research into germ cell antimutagenicity is warranted, with findings comparable to bone marrow studies.