Mixture Analysis of Associations between Occupational Exposure to Polycyclic Aromatic Hydrocarbons and Sperm Oxidative DNA Damage.

Abstract

OBJECTIVE\nThis study aimed to determine (i) associations between levels of the polycyclic aromatic hydrocarbon (PAH) mixture with 16 targeted PAH compounds in the personal breathing zone area and sperm oxidative DNA damage, (ii) associations between levels of individual PAH compounds and sperm oxidative DNA damage, (iii) oxidative stress as the mode of action for the genotoxic effects on sperm, and (iv) any dose-response relationship between exposure to the PAH mixture and/or individual PAH compounds and sperm oxidative DNA damage.\n\n\nMETHODS\nSixteen targeted PAH compounds in the personal breathing zone area of 38 coke-oven workers and 24 control subjects were quantified using gas chromatography-mass spectrometry. Sperm oxidative damage and status were evaluated by measuring levels of sperm 7,8-dihydro-8-oxoguanie (8-oxodGuo), seminal malondialdehyde (MDA) and seminal reactive oxygen species (ROS). Bayesian kernel machine regression with hierarchical variable selection process was employed to determine associations of the PAH mixture and the biomarkers of sperm oxidative damage. A novel grouping approach needed for the hierarchical variable selection process was developed based on PAH bay region and molecular weight.\n\n\nRESULTS\nThe PAH mixture exhibited a positive trend with increased sperm 8-oxodGuo levels at their lower percentiles (25th-50th). The exposure of the PAH mixture was associated with increased MDA levels in sperm. Bay and bay-like regions of the PAH mixture were the most important group for estimating the associations between the PAH mixture and sperm oxidative stress status. Benzo[a]anthracene was the main individual PAH compound that was associated with increased MDA levels.\n\n\nCONCLUSION\nSperm oxidative DNA damage induced by occupational exposure to the PAH mixture had a suggestive association with increased MDA levels in coke-oven workers. Finally, the study identified that the individual PAH compound, benzo[a]anthracene, was the primary driver for the suggestive association between the PAH mixture and sperm oxidative damage.