G6PD缺陷对1,4-苯醌致K562细胞DNA甲基化的影响及其机制

doi:10.3969/j.issn.1004-616x.2019.03.003

Abstract

Abstract: OBJECTIVE: To investigate the effect of 1,4-benzoquinone (1,4-BQ) exposure and G6PD deficiency on DNA methylation in K562 cells. METHODS:G6PD-deficient K562 cells and normal cells were treated with 0,10,20 μmol/L 1,4-BQ solution for 12,24 and 48 hours. Relative levels of DNA methylation in cell genome were detected by colorimetric analysis and expression levels of DNMT1,DNMT3a and DNMT3b were detected by real-time fluorescence quantitative PCR (qPCR). Expression levels of DNMT1 and DNMT3a proteins were detected by Western blot.RESULTS:The genomic DNA methylation levels in the normal K562 cells were increased in the 10 and 20 μmol/L dose groups (P<0.05) but not by the 20 μmol/L dose group at 24 hour. The methylation levels in the GPPD-deficient K562 cells were significantly higher than that in normal cells for all exposed groups (P<0.05). After 1,4-BQ exposure, the expression levels of DNMT1, DNMT3a, DNMT3b mRNA and DNMT1, DNMT3a proteins in G6PD-deficient cells were higher than those in normal cells (P<0.05). After the addition of GSH, the relative levels of whole genome DNA methylation, DNMTs mRNA and protein expression levels of G6PD-deficient cells and normal cells became non-statistically significant. CONCLUSION:G6PD deficiency might have increased the level of oxidative stress by inhibiting GSH synthesis,which ultimately led to an increase in the production of DNMTs and an increase in the DNAmethylation level of the whole genome.

Key words: 1,4-benzoquinone, DNA methylation, DNA methyltransferase, glutathione

CLC Number:

R135.1

ZHANG Mengying, WANG Boshen, ZHANG Hong, PU Yuepu, YIN Lihong, ZHANG Juan. Effect from 1,4-benzoquinone exposure on DNA methylation in G6PD deficient K562 cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(3): 186-192.

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Effect from 1,4-benzoquinone exposure on DNA methylation in G6PD deficient K562 cells

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