Methylation of PARP-1 promoter involved in the regulation of benzene-induced decrease of PARP-1 mRNA expression.
Benzene is an established hematotoxic carcinogen which can cause leukemia. DNA damage and disorder of repair capacity are the crucial mechanisms in leukemogenesis of benzene. DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-aza) and histone deacetylase inhibitor, trichostatin A (TSA) are two kinds of key epigenetic modification reagents. The mRNA expression of poly(ADP-ribose) polymerases-1 (PARP-1), a pivotal repair gene, has been decreased by benzene. However, the effect of epigenetic modification on benzene-induced low PARP-1 expression has not been reported. In this study, lymphoblastoid cell line F32 was incubated by benzene and then further treated with 5-aza and TSA, alone or in combination. The reverse transcription-polymerase chain reaction and methylation-specific PCR were performed to examine the mRNA expression and methylation status of PARP-1, respectively. Results showed a dramatic decrease of PARP-1 mRNA expression and a simultaneously obvious increase in the level of PARP-1 methylation in benzene-treated cells compared to the control. Further, the PARP-1 mRNA expression was restored and the level of PARP-1 methylation was also reduced following epigenetic inhibitors, 5-aza and TSA, alone or in combination treatments. Taken together, methylation of PARP-1 promoter might be involved in the regulation of benzene-induced decrease of PARP-1 mRNA expression.
School of Public Health and Family Medicine, Capital Medical University, Beijing 100069, China.
Ai
A
Gao
Xin
X
Zuo
Qingjie
Q
Liu
Xue
X
Lu
Wei
W
Guo
Lin
L
Tian
D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001554:Benzene / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D019175:DNA Methylation / Q000187:drug effects*; D000077209:Decitabine; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008780:Methyltransferases / Q000037:antagonists & inhibitors; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism
D002273:Carcinogens; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012333:RNA, Messenger; C012589:trichostatin A; D000077209:Decitabine; D008780:Methyltransferases; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D001554:Benzene; D001374:Azacitidine