title: Epigenetic modification involved in benzene-induced apoptosis through regulating apoptosis-related genes expression.
abstract: 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.
authors.affiliation: School of Public Health and Family Medicine, Capital Medical University, Beijing 100069, Peoples Republic of China.
authors.forename: Ai
authors.initials: A
authors.lastname: Gao
authors.forename: Xin
authors.initials: X
authors.lastname: Zuo
authors.forename: Shanshan
authors.initials: S
authors.lastname: Song
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Lin
authors.initials: L
authors.lastname: Tian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001374:Azacitidine / Q000031:analogs & derivatives*; D001554:Benzene / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology*; D002478:Cells, Cultured; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002273:Carcinogens; D006877:Hydroxamic Acids; D012333:RNA, Messenger; C012589:trichostatin A; D001554:Benzene; D001374:Azacitidine