Epigenetic modification involved in benzene-induced apoptosis through regulating apoptosis-related genes expression
Benzene is an establisned haematotoxic and genotoxic carcinogen DNA methyltransferase inhibitor,5-aza (5-aza-2”-eoxycytidine) and histone deacetylase inhibitor,TSA (trichoslatin A) are two kinds of key epigenetic modification reagents Although apoptosis has been considered as the key cytotoxicity mechanism,the effects of these epigenetic reagents on benzene-induced apoptosis have not been reported (i)n this study,BMCs (bone marrow cells) from rats were incubated with benzene and then with either 5-aza,TSA alone or the combination of the two drugs Apoptosis and mRNAexpression were detected by annexin V/PI (propidium iodide) staining assay and real-time PCR respectively(,) Results showed that benzene caused cell apoptosis accompanied with bcl-2 mRNA decrease caspase-3 and bax mRNA increase Moreover,benzene induced apoplosis and the decrease of bcl-2 mRNA were both reversed by both 5-aza and ISA but the role of TSA was significantly larger than 5-aza More interestingly(,) these increases in benzene-induced caspase-3 and bax mRNA expression were obviously suppressed by 5-aza but not by TSA (,)In conclusion 5-aza inhibited benzene-induced apoptosis through down-regulating of caspase-3 and bax and up-regulating bcl-2 mRNA expression whereas the effect of TSA on apoptosis dominatingly affected bcl 2mRNA expression and 5-aza together with TSA had no synergic effect on benzene induced apoptosis.
5-aza-2-deoxycy(ti)dine apop(i)osis benzene real-time PCR trichostatin A
Ai Gao Xin Zuo Shanshan Song Wei Guo Lin Tian
School of Public Health and Family Medicine Capital Medical University, Beljing 100069, People”s Republic of China
国内会议
北京
英文
261-266
2012-09-01（万方平台首次上网日期，不代表论文的发表时间）