1-Hydroxypyrene glucuronide and 8-hydroxy-2’-deoxyguanosine as complementary biomarkers bridging polycyclic aromatic hydrocarbon exposure to carcinogenic risk: Mechanistic and epidemiological perspectives

Abstract

Background: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental carcinogens that contribute to cancer development through oxidative stress, DNA damage, and genomic instability. However, current biomonitoring approaches often assess exposure and biological effects independently, limiting risk assessment and mechanistic interpretation. Aim: This review evaluates the complementary roles of urinary 1-hydroxypyrene glucuronide (1-OHPG) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) as integrated biomarkers linking PAH exposure with early carcinogenic events. Methods: A narrative review of published literature was conducted, focusing on PAH metabolism, the biological significance of 1-OHPG and 8-OHdG, epidemiological evidence assessing both biomarkers, sources of heterogeneity, methodological limitations, and future directions for precision environmental carcinogenesis. Results: Urinary 1-OHPG is a validated biomarker of internal PAH exposure, whereas urinary 8-OHdG reflects oxidative DNA damage induced by reactive oxygen species generated during PAH metabolism. Epidemiological studies generally demonstrate positive associations between elevated 1-OHPG and 8-OHdG in occupationally and environmentally exposed populations. Nevertheless, biological variability, mixed exposures, analytical differences, and predominantly cross-sectional study designs contribute to heterogeneity. Integrating these biomarkers provides a more comprehensive exposure–effect framework for interpreting PAH-induced carcinogenic processes. Conclusion: The combined assessment of urinary 1-OHPG and 8-OHdG strengthens biomonitoring by simultaneously evaluating internal PAH exposure and early molecular damage. This integrated framework has the potential to improve environmental cancer risk assessment and support precision environmental health. Relevance for patients: Integrated biomonitoring of urinary 1-OHPG and 8-OHdG may facilitate earlier identification of individuals at increased risk from chronic PAH exposure, enabling targeted prevention, improved surveillance, and informed public health interventions.