New insight into intrachromosomal deletions induced by chrysotile in the gpt delta transgenic mutation assay.

Environ Health Perspect

Center for Radiological Research, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA.

Published: January 2007

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 1 microg/cm(2) increased by > 5-fold relative to nontreated controls (p < 0.005). Mutation spectra analyses showed that the ratio of 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 y-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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1797839PMC
http://dx.doi.org/10.1289/ehp.9425DOI Listing

Publication Analysis

Top Keywords

induced chrysotile
12
gpt delta
12
delta transgenic
12
asbestos fibers
12
induced
8
chrysotile fibers
8
fibers gpt
8
transgenic mouse
8
lambda mutants
8
mutants losing
8

Similar Publications

Asbestos minerals have been widely exploited due to their physical-chemical properties, and chrysotile asbestos has accounted for about 95% of all asbestos commercially employed worldwide. The exposure to chrysotile, classified like other five amphibole asbestos species as carcinogenic to humans, represents a serious occupational and environmental hazard. Nevertheless, this mineral is still largely employed in about 65% of the countries worldwide, which still allow its "safe use".

View Article and Find Full Text PDF

Background: Today, many research groups in the world are struggling to fully understand the mechanisms leading to the carcinogenesis of hazardous mineral fibres, like asbestos, in view of devising effective cancer prevention strategies and therapies. Along this research line, our work attempts the completion of a model aimed at evaluating how, and to what extent, physical-crystal-chemical and morphological parameters of mineral fibres prompt adverse effects leading to carcinogenesis.

Methods: toxicology tests that deliver information on the 10 key characteristics of carcinogens adopted by the International Association for Research on Cancer (IARC) have been systematically collected for a commercial chrysotile, standard UICC crocidolite and wollastonite.

View Article and Find Full Text PDF

Asbestos fiber exposure triggers chronic inflammation and cancer. Asbestos fibers can adsorb different types of proteins. The mechanism of this adsorption, not yet completely understood, has been studied in detail mainly with serum albumin and was shown to induce structural changes in the bound protein.

View Article and Find Full Text PDF
Article Synopsis
  • The study investigates the impact of long-term exposure to chrysotile and crocidolite on microRNAs (miRNAs) and the expression of genes related to epithelial mesenchymal transition (EMT) in human pleural mesothelial cells.
  • Using RT-qPCR, the researchers analyzed gene expression in mesothelioma cells and normal mesothelial cells after treatment with asbestos fibers, comparing different treatment groups (chrysotile, crocidolite, control).
  • Results showed increased expression of EMT-related genes (like Vimentin and Twist) and decreased expression of E-cadherin in mesothelioma cells, along with abnormal changes in specific miRNAs that were directly correlated with EMT processes.
View Article and Find Full Text PDF
Article Synopsis
  • * The cumulative exposure levels to chrysotile were measured, with most workers being young males, and the inhalation levels ranged widely, with a median exposure of 0.0018 f/mL.years.
  • * Findings revealed a low prevalence of cough (11.7%) and an even lower lung cancer mortality risk (less than 1%), suggesting that the workers faced minimal cancer risks due to their lower exposure levels.*
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!