Methylation of PARP-1 promoter involved in the regulation of benzene-induced decrease of PARP-1 mRNA expression

Abstract

Benzene is an established hematotoxic carcinogen which can cause leukemia. DNA damage and disorder of repair capacity are the crucial mechanisms in leukemogenesis of benzene. DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-aza) and histone deacetylase inhibitor, trichostatin A (TSA) are two kinds of key epigenetic modification reagents. The mRNA expression of poly(ADP-ribose) polymerases-1 (PARP-1), a pivotal repair gene, has been decreased by benzene. However, the effect of epigenetic modification on benzene-induced low PARP-1 expression has not been reported. In this study, lymphoblastoid cell line F32 was incubated by benzene and then further treated with 5-aza and TSA, alone or in combination. The reverse transcription-polymerase chain reaction and methylation-specific PCR were performed to examine the mRNA expression and methylation status of PARP-1, respectively. Results showed a dramatic decrease of PARP-1 mRNA expression and a simultaneously obvious increase in the level of PARP-1 methylation in benzene-treated cells compared to the control. Further, the PARP-1 mRNA expression was restored and the level of PARP-1 methylation was also reduced following epigenetic inhibitors, 5-aza and TSA, alone or in combination treatments. Taken together, methylation of PARP-1 promoter might be involved in the regulation of benzene-induced decrease of PARP-1 mRNA expression.