Radon-induced demethylation of Cdk2 CpG island in the rat lung

다국어 초록 (Multilingual Abstract)

Radon exposure has been linked to lung carcinogenesisin both human and animal studies. The identificationof sequential changes in DNA methylation duringtumour progression and the elucidation of their interplaywith genetic changes will broaden our molecular understandingof this disease. Rats were exposed to 120 or 400working level months (WLM) of radon, lung pathologicalchanges were examined by haematoxylin and eosin staining,lung single cell suspension cell cycles were detected byflow cytometry, lung cell cycle regulated gene (Cdkn2a,P53, Cdk4/2, Mdm4/2 and Rb1 genes) expression wasquantified by real-time PCR and methylation of CpG islandsin the promoters of cell cycle-regulated genes were detectedby bisulfite sequencing PCR. The alveolar walls of rat lungsafter exposured to radon exhibited papillae and the lungbronchial epithelial cells stained positively for proliferatingcell nuclear antigen. The bronchial epithelial cells displayedsome hyperplasia after challenged by 400 WLM of radon.
Moreover, G1 arrest decreased; Rb1, Mdm2/4, and Cdk2/4expression decreased and Cdk2 was demethylated at thesecond and sixth CpG loci from base pairs 3092704 to3092953 of chromosome 7. Cdk2 demethylation may beapplicable as a biomarker of early lung damage that wasinduced by radon and other environmental carcinogens.

참고문헌 (Reference)

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