1,4-benzoquinone-induced STAT-3 hypomethylation in AHH-1 cells: role of oxidative stress

The objectives of this study were to elucidate the regulatory mechanism of the hypomethylated STAT3 involved in benzene toxicity in vitro. As 1,4-benzoquinone (1,4-BQ) is one of benzene's major toxic metabolites, AHH-1 cells were treated by 1,4-BQ for 24hours with or without pretreatment of the antioxidant a–LA or the methyltransferase inhibitor, 5-Aza-2' deoxycytidine (5-aza). The cell viability was investigated using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. ROS was determined via 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) flow cytometric assays. The level of oxidative stress marker 8-OHdG was measured by enzyme-linked immunosorbent assay. Methylation-specific PCR was used to detect the methylation status of STAT3. Results indicated the significantly increasing expression of ROS and 8-OHdG which accompanied with STAT3 hypomethylation in 1,4-BQ-treated AHH-1 cells. α-LA suppressed the expression of both ROS and 8-OHdG, simultaneously reversed 1,4-BQ-induced STAT3 hypomethylation. However, although the methylation inhibitor, 5-aza reduced the expression level of ROS and 8-OHdG, but had no obvious inhibiting effect on STAT3 methylation level. Taken together, oxidative stress are involved 1,4-BQ-induced STAT3 methylation expression.
Source: Toxicology Reports - Category: Toxicology Source Type: research