|Cancer||Cell death||Cell cycle||Cytoskeleton||Exo/endocytosis||Differentiation||Division||Organelles||Signalling||Stem cells||Trafficking|
Epigenetic modification involved in benzene-induced apoptosis through regulating apoptosis-related genes expression
Ai Gao1, Xin Zuo1, Shanshan Song, Wei Guo and Lin Tian2
School of Public Health and Family Medicine, Capital Medical University, Beijing 100069, Peoples Republic of China
Benzene is an established haematotoxic and genotoxic carcinogen. DNA methyltransferase inhibitor, 5-aza (5-aza-2′-eoxycytidine) and histone deacetylase inhibitor, TSA (trichostatin 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. In 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 mRNA expression 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 apoptosis and the decrease of bcl-2 mRNA were both reversed by both 5-aza and TSA, 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-2 mRNA expression, and 5-aza together with TSA had no synergic effect on benzene-induced apoptosis.
Key words: 5-aza-2′-deoxycytidine, apoptosis, benzene, real-time PCR, trichostatin A
Abbreviations: 5-aza, 5-aza-2′-deoxycytidine, BMCs, bone marrow cells, CT, cycle threshold, DNMT, DNA methyltransferase, HDAC, histone deacetylase, PI, propidium iodide, TSA, trichostatin A
1Ai Gao and Xin Zuo contributed equally to this work.
2To whom correspondence should be addressed (email firstname.lastname@example.org).
Received 15 April 2010/9 September 2010; accepted 14 December 2010
Published as Cell Biology International Immediate Publication 14 December 2010, doi:10.1042/CBI20100256
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