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Chromosomal aberration of asbestos-induced malignant mesothelioma in rats

ABSTRACT: Exposure to asbestos is a risk for malignant mesothelioma in humans. We carried out array comparative genomic hybridization (CGH) analysis in a rat model by repeated intraperitoneal injections of three types of asbestos including chrysotile, crocidolite and amosite. We found a common chromosomal deletion mapped to the chromosome 5q32 locus, containing the genes encoding tumour suppressor genes CDKN2A/2B/ARF. Homozygous deletion of CDKN2A/2B/ARF was observed in the majority (92.6%) of the rat MM samples.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE36577 | GEO | 2012/08/14

SECONDARY ACCESSION(S): PRJNA153737

REPOSITORIES: GEO

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Project description:Recent in vivo studies reported that inhaled carbon nanotube distribute in the alveolar region resulting in an acute inflammation, progressive fibrotic response and particle accumulation at the bronchoalveolar junction with low clearance. With similar biopersistence and shape as asbestos, a known lung carcinogen, growing concern has arisen for elevated risk of carbon nanotube-induced lung carcinogenesis; however few studies have evaluated long-term human health risks associated with chronic pulmonary carbon nanotube exposures compared to asbestos. To address this knowledge gap, we conducted subchronic in vitro exposures of dispersed single walled carbon nanotube, multi-walled carbon nanotube and crocidolite asbestos to human small airway epithelial cells to assess their neoplastic transformation potential. Subchronic single-, multi-walled carbon nanotube and asbestos exposures caused human lung cell neoplastic transformation exhibited by increased proliferation, anchorage-independent growth, invasion and angiogenesis. Whole genome profiling and protein expression analyses showed that carbon nanotube-induced transformation mechanism(s) was largely different from asbestos-related inflammatory signaling, suggesting specific carbon nanotube-induced carcinogenic potential. This study provides novel carbon nanotube and asbestos toxicogenomic information for risk assessment and an in vitro model to evaluate transformation potential of carbon nanotubes and other nanoparticles. Whole genome expression profiling was conducted on human immortalized small airway epithelial cells (SAEC-hTERT) following 6 month in vitro chronic exposure to six separate treatments to assess differences in carbon nanotube (CNT) vs. asbestos potential tumorigenesis signaling. Dispersed single wall CNT (D-SWCNT), multi-wall CNT (D-MWCNT), ultrafine carbon black (D-UFCB), crocidolite asbestos (ASB) and saline (SAL) exposed cells were compared to SurvantaM-BM-. dispersant (DISP) passage control cells. Each treatment possessed 3 biological cDNA replicates. One technical replicate was performed per biological sample.

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Chromosomal aberration of asbestos-induced malignant mesothelioma in rats

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