Epigenetic mediated transcriptional activation of PARP-1 participates in silica-associated malignant transformation of human bronchial epithelial cells.

Silica was listed as a human carcinogen by International Agency for Research on Cancer (IARC) in 1996. However, the molecular mechanisms to induce cancer are not understood yet. Our recent published study showed that silica inhibited the expression of poly(ADP-ribose) polymerases-1 (PARP-1) mRNA. However, the mechanisms responsible for low PARP-1 expression have not yet been elucidated. In this study, the human bronchial epithelial cells (16HBE) were treated with 300 microg/ml silicon dioxide for 35 passages, the mode of silica-associated malignant transformation of human bronchial epithelial cells (M-16HBE) was established and identified by soft agar assay and nude mouse tumorigenesis. The mRNA expression and methylation status of PARP-1 in M-16HBE with or without treatment of the cytosine methylation inhibitor 5-aza-2'-deoxycytidine (5-aza) were detected by real-time PCR and methylation-specific PCR (MSP), respectively. The data showed that silica decreased PARP-1 expression at the transcriptional levels in M-16HBE and the above epigenetic inhibitors reversed the transcriptional inhibition of PARP-1 through the demethylation of PARP-1, suggesting that the epigenetic mediated transcriptional activation of PARP-1.