Capital Medical University, Beijing, China.
Toxicol Lett. 2010 Apr 1;193(3):236-41. doi: 10.1016/j.toxlet.2010.01.017. Epub 2010 Feb 1.
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.
二氧化硅于 1996 年被国际癌症研究机构（IARC）列为人类致癌物。然而，其诱导癌症的分子机制尚不清楚。我们最近的研究表明，二氧化硅抑制聚（ADP-核糖）聚合酶-1（PARP-1）mRNA 的表达。然而，导致 PARP-1 表达降低的机制尚未阐明。在这项研究中，用 300μg/ml 的二氧化硅处理人支气管上皮细胞（16HBE）35 代，通过软琼脂实验和裸鼠致瘤实验建立和鉴定了与人支气管上皮细胞恶性转化相关的二氧化硅（M-16HBE）。通过实时 PCR 和甲基化特异性 PCR（MSP）分别检测了 M-16HBE 中 PARP-1 的 mRNA 表达和甲基化状态，以及是否用胞嘧啶甲基化抑制剂 5-氮杂-2'-脱氧胞苷（5-aza）处理。结果表明，二氧化硅在 M-16HBE 中降低了 PARP-1 的转录水平，而上述表观遗传抑制剂通过 PARP-1 的去甲基化逆转了 PARP-1 的转录抑制，提示 PARP-1 的表观遗传介导的转录激活。
