H3K9me2 regulates the transcription of nucleotide excision repair related genes in DNA damage of normal hepatocytes induced by sodium arsenic / 中华地方病学杂志

ABSTRACT

Objective:To investigate the effects of different doses of sodium arsenic (NaAsO 2) on mRNA transcription levels of nucleotide excision repair (NER) related genes in normal hepatocytes (L-02 cells) and the modification levels of histone H3 ninth lysine dimethylization (H3K9me2) in the promoter region. Methods:L-02 cells were treated with 0 (the control group) , 5, 10 and 20 μmol/L NaAsO 2 for 24 h ( n = 3). Single cell gel electrophoresis (SCGE) was used to detect DNA damage [Olive tail distance (OTM) and Tail DNA percentage (Tail DNA%)] in L-02 cells. The mRNA expression levels of Xeroderma pigmentosum (XP) gene A (XPA), XP gene D (XPD) and XP gene F (XPF) were detected by real-time fluorescence quantitative PCR. The modification levels of H3K9me2 in XPA, XPD and XPF gene promoter regions (CHIP1 and CHIP2) were detected by quantitative chromatin immunoprecipitation. Results:OTM and Tail DNA% were positively correlated with arsenic doses (in the control and 5, 10 and 20 μmol/L arsenic exposure groups, the values were 0.35 ± 0.09, 0.56 ± 0.18, 3.18 ± 0.31, 4.52 ± 0.55, 0.72 ± 0.05, 1.34 ± 0.26, 3.93 ± 0.43, 5.47 ± 0.65, respectively, r = 0.927, 0.948, P < 0.05). Compared with the control group, the mRNA expression levels of XPA, XPD and XPF in L-02 cells of 10 and 20 μmol/L arsenic exposure groups were significantly lower ( P < 0.05). Compared with the control group, the enrichment levels of H3K9me2 in XPA, XPD and XPF gene promoter regions (CHIP1 and CHIP2) in L-02 cells of 20 μmol/L arsenic exposure group were significantly higher ( P < 0.05). Conclusion:Arsenic may inhibit the transcription of NER related genes by increasing the enrichment level of H3K9me2 in the promoter regions (CHIP1 and CHIP2) of NER related genes, thereby reduce the DNA damage repair ability of L-02 cells, resulting in the aggravation of DNA damage.