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

BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.