Journal
ENVIRONMENTAL HEALTH PERSPECTIVES
Volume 115, Issue 1, Pages 87-92Publisher
US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
DOI: 10.1289/ehp.9425
Keywords
chrysotile asbestos; gpt delta transgenic mutation system; kilobase-sized mutation; oxyradicals; gamma-H2AX
Funding
- NIEHS NIH HHS [R01 ES005786, ES 09089, P30 ES009089, ES 10349, ES 05786, F32 ES005786, P42 ES010349] Funding Source: Medline
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P42ES010349, F32ES005786, R01ES005786, P30ES009089] Funding Source: NIH RePORTER
Ask authors/readers for more resources
BACKGROUND: Genotoxicity is often a prerequisite to the development of malignancy. Considerable evidence has shown that exposure to asbestos fibers results in the generation of chromosomal aberrations and multilocus mutations using various in vitro approaches. However, there is less evidence to demonstrate the contribution of deletions to the mutagenicity of asbestos fibers in vivo. OBJECTIVES: In the present study, we investigated the mutant fractions and the patterns induced by chrysotile fibers in gpt delta transgenic mouse primary embryo fibroblasts (MEFs) and compared the results obtained with hydrogen peroxide (H2O2) in an attempt to illustrate the role of oxyradicals in fiber mutagenesis. RESULTS: Chrysotile fibers induced a dose-dependent increase in mutation yield at the redBA/gam loci in transgenic MEF cells. The number of lambda mutants losing both redBA and gam loci induced by chrysotiles at a dose of I mu g/cm(2) increased by > 5-fold relative to nontreated controls (p < 0.005). Mutation spectra analyses showed that the ratio lambda mutants losing the redBA/gam region induced by chrysotiles was similar to those induced by equitoxic doses of H2O2. Moreover, treatment with catalase abrogated the accumulation of gamma-H2AX, a biomarker of DNA double-strand breaks, induced by chrysotile fibers. CONCLUSIONS: Our results provide novel information on the frequencies and types of mutations induced by asbestos fibers in the gpt delta transgenic mouse mutagenic assay, which shows great promise for evaluating fiber/particle mutagenicity in vivo.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available