The effects and potential mechanisms of essential metals on the associations of polycyclic aromatic hydrocarbons with blood cell-based inflammation markers.

ABSTRACT

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are well-acknowledged pro-inflammatory chemicals, but their associations with blood cell-based inflammatory biomarkers need further investigation. Moreover, the effects and mechanisms of essential metals on PAH-related inflammation remain poorly understood. OBJECTS To elucidate the associations of PAHs on inflammatory biomarkers, as well as the effects and mechanisms of essential metals on these associations. METHODS: A cross-sectional study was conducted on 1388 coke oven workers. We analyzed the modification effects of key essential metal(s) on PAHs-inflammatory biomarkers associations. To explore the possible mechanisms from an inflammation perspective, we performed a bioinformatic analysis on the genes of PAHs and essential metals obtained from the Comparative Toxicogenomics Database (CTD) and performed a mediation analysis. RESULTS: We observed associations of PAHs and essential metals with lymphocyte-to-monocyte ratio (LMR) (P < 0.05). PAH mixtures were inversely associated with LMR (ßQGC-index = -0.18, P < 0.001), with 1-hydroxypyrene (1-OH-Pyr) being the most prominent contributor (weight = 63.37%), whereas a positive association between essential metal mixtures and LMR was observed (ßQGC-index = 0.14, P < 0.001), with tin being the most significant contributor (weight = 51.61%). An inverse association of 1-OH-Pyr with LMR was weakened by increased tin exposure (P < 0.05). The CTD database showed that PAHs and tin compounds co-regulated 22 inflammation-associated genes, but they regulated most genes in opposite directions. Further identified the involvement of oxidative stress and mediation analysis showed that the mediation effect of 8-hydroxydeoxyguanosine (8-OHdG) on 1-OH-Pyr-LMR association presented heterogeneity between low and high tin tertile groups (I2 = 37.84%). CONCLUSION: 1-OH-Pyr and tin were significantly associated with LMR. Modification effects indicated that the inverse association of 1-OH-Pyr with LMR was mitigated with an increase in tin. The mediation effect of 8-OHdG on the inverse association of 1-OH-Pyr with LMR may be partially dependent on tin.