Effect of exposure to phthalates on association of polycyclic aromatic hydrocarbons with 8-hydroxy-2'-deoxyguanosine.

Abstract

Although polycyclic aromatic hydrocarbons (PAHs) and phthalates separately related to oxidative DNA damage have been reported, the joint effect of them on oxidative DNA damage need to be evaluated. In this pilot study, 106 participants were recruited from the community-dwelling residents (n=1240) of Wuhan city, China. Each individual provided three continuous days of spot urine samples for measuring the urinary monohydroxylated PAHs (OH-PAHs), phthalates metabolites and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the two seasons. Linear mixed effect model and Bayesian Kernel Machine Regression (BKMR) were used to analyze joint effect of urinary PAHs and phthalates metabolites on urinary 8-OHdG levels. We measured cellular and mitochondrial reactive oxygen species (ROS), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) levels as well as IL-6 and IL-8 secretions by the corresponding commercial kits in HepG2 cells treated with di (2-ethylhexyl) phthalate (DEHP, 62.5, 125.00, 250.00, 500.00 or 1000.00μM) alone, benzo[a]pyrene (BaP, 50.00μM) alone or both DEHP and BaP. Linear mixed effect model showed that each of urinary PAHs metabolite was positively associated with urinary 8-OHdG levels; urinary level of mono (2-ethylhexyl) phthalate or monoisononyl phthalate was positively associated with urinary 8-OHdG levels; BKMR model indicated that a positive association of eight OH-PAHs with urinary 8-OHdG levels, nine urinary phthalates metabolites enhanced the association. We found that DEHP at the indicated concentration plus 50.00μM BaP increased cellular and mitochondrial ROS levels, IL-6 and IL-8 secretions at 24 and 48h as well as MDA levels and GSH-Px activities at 48h, compared to the solvent control. Exposure to certain dose phthalates may attenuate the positive association of PAHs exposure with oxidative DNA damage in the body. DEHP at the certain concentrations enhanced BaP-induced mitochondrial ROS, pro-inflammatory response and the activation of the antioxidant defense system in HepG2 cells.