Methylation of RAR-β2, RASSF1A, and CDKN2A genes induced by nickel subsulfide and nickel-carcinogenesis in rats.

OBJECTIVE To investigate the expression variation of RAR-β2, RASSF1A, and CDKN2A gene in the process of nickel-induced carcinogenesis. METHODS Nickel subsulfide (Ni(3)S(2)) at dose of 10 mg was given to Wistar rats by intramuscular injection. The mRNA expression of the three genes in induced tumors and their lung metastasis were examined by Real-time PCR. The methylation status of the 5' region of these genes were detected by Quantitative Real-time methylation specific PCR. RESULTS The mRNA expressions of the three genes both in muscle and lung tumor were decreased distinctly in comparison with normal tissue. But hypermethylation was found only in muscle tumor. CONCLUSION These findings suggest that loss of function or decrease of RAR-β2, RASSF1A, and CDKN2A, as well as the hypermethylation of 5' region of these genes, are related with nickel exposure.