1-Hydroxypyrene Glucuronide & 8-Hydroxy-2'-deoxyguanosine: A Key Biomarker Bridging Polycyclic Aromatic Hydrocarbons (PAHs) Exposure to Malignancy— Mechanistic and Epidemiological Perspectives

Polycyclic aromatic hydrocarbons (PAHs) are pervasive environmental carcinogens whose health impacts depend on both exposure burden and downstream molecular damage. However, a major limitation in current risk assessment is the lack of integrated biomarker strategies that link exposure to early carcinogenic events. This review focuses on two critical and complementary biomarkers; 1-Hydroxypyrene Glucuronide (1-OHPG), a validated indicator of internal PAH exposure, and 8-Hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage and mutagenesis. While these biomarkers are individually well-established, their combined application remains underexplored. Mechanistically, PAH metabolism generates reactive intermediates and reactive oxygen species that induce DNA lesions, with 8-hydroxy-2'-deoxyguanosine reflecting cumulative oxidative genomic injury. Epidemiologically, elevated levels of both biomarkers have been associated with increased cancer risk in exposed populations, yet they are often assessed independently, limiting their predictive power. This review critically evaluates existing evidence and highlights the disconnect between exposure assessment and biological effect monitoring. It proposes that the simultaneous integration of 1-hydroxypyrene glucuronide and 8-hydroxy-2'-deoxyguanosine provides a more robust framework for linking PAH exposure to carcinogenic outcomes. Bridging this gap could significantly enhance early detection, mechanistic interpretation, and risk stratification in PAH-related malignancies.