Oxidative Stress and Redox Transcriptomic Signatures Associated with Coexposure to Emerging Contaminants

Abstract

Despite ubiquity of contaminants of emerging concern (CECs), biological consequences of combined exposure remain poorly understood, particularly regarding oxidative stress and related redox-sensitive molecular responses. We quantified 64 urinary CECs across seven chemical classes (bisphenol analogues, parabens, synthetic phenolic antioxidants, antimicrobials, organophosphate esters, neonicotinoids, and ultraviolet filters) and two oxidative stress biomarkers [8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostaglandin F2α (8-isoPGF2α)] in 142 Chinese adults. Single-chemical associations were assessed using generalized linear models, while joint associations were evaluated by elastic net regression and quantile g-computation. By integrating leukocyte mRNA sequencing profiles, we identified redox-related transcriptional signatures linking CEC exposure to oxidative stress. Fourteen and 13 CECs were associated with elevated 8-OHdG and 8-isoPGF2α, respectively. Mixture analyses showed positive associations of combined CEC exposure with both biomarkers. Key contributors in mixture models included octabenzone, bisphenol A, tris(2-chloroisopropyl) phosphate, and acetamiprid for 8-OHdG and octabenzone, triisobutyl phosphate, and 2,6-di-tert-butyl-4-hydroxy-4-methylcyclohexa-2,5-dien-1-one for 8-isoPGF2α. Transcriptomic integration indicated mixture-associated oxidative stress was accompanied by coordinated redox-sensitive gene expression changes, with shared enrichment of inflammatory and stress-response pathways (including Toll-like receptor and MAPK signaling) across chemical classes. Notably, SYT1 and CCNP emerged as recurrent transcriptomic candidates linking CEC exposure with oxidative stress, supporting coordinated transcriptional response under real-world CEC coexposure.