Polycyclic aromatic hydrocarbon exposure and mitochondrial DNA copy number: Opposing roles of oxidative stress and...

Previous studies indicate that exposure to polycyclic aromatic hydrocarbons (PAHs) may impair mitochondrial function and induce oxidative stress and inflammation. However, the associations of PAH exposure with mitochondrial DNA and related biological responses remain largely unexplored. In this study, we assessed the association between urinary hydroxylated polycyclic aromatic hydrocarbon metabolites (OH-PAHs) and blood mitochondrial DNA copy number while exploring the potential mediating roles of oxidative stress and inflammatory markers. We determined urinary concentrations of OH-PAHs, 8-hydroxy-2'-deoxyguanosine, and 8-hydroxyguanosine, and measured white blood cell count in whole blood of 385 participants. The relative mitochondrial DNA copy number was assessed by real-time quantitative polymerase chain reaction using two mitochondrial target genes normalized against three reference genes. Urinary OH-PAHs and oxidative stress markers showed a significant increasing trend with age, whereas white blood cell counts were not significantly associated with age. Multivariable linear regression models demonstrated that 3-hydroxyfluorene and 4-hydroxyphenanthrene were consistently positively associated with mitochondrial DNA abundance. Mixture effect analysis indicated that higher quantiles of urinary concentrations of OH-PAHs were associated with increased mitochondrial DNA copy number across different normalization genes. Mediation analysis showed that urinary OH-PAHs were positively associated with mitochondrial DNA copy number, yet the indirect effect mediated through oxidative stress was in the opposite direction to the direct effect. In contrast, the indirect effect through inflammation was consistent with the direct effect. The results indicated that oxidative stress exhibited a suppression effect on the association between PAH exposure and mitochondrial DNA copy number, whereas inflammatory markers acted as mediators in these associations.