Molecular Mechanisms of Arsenic-Induced Hepatotoxicity and Epigenetic Disruption in Communities with Groundwater Contamination in Plateau State

Arsenic contamination of groundwater is a recognised public health hazard in mining communities across Plateau State, North Central Nigeria, and its molecular hepatotoxic effects, particularly via epigenetic disruption, remain poorly characterised in indigenous African populations. This study investigates the molecular mechanisms of arsenic-induced hepatotoxicity, focusing on oxidative DNA damage, mitochondrial dysfunction, and promoter methylation changes in detoxification genes in exposed community members compared to unexposed controls. A cross-sectional design was employed across two arsenic-impacted communities in Jos South and Barkin Ladi LGAs, recruiting 80 arsenic-exposed adults and 80 unexposed controls. Urinary inorganic arsenic, monomethylarsonic acid, and dimethylarsinic acid were quantified by hydride generation atomic absorption spectrophotometry. Hepatic biomarkers including ALT, AST, and GGT were measured alongside mitochondrial membrane potential assessed in peripheral blood mononuclear cells. Methylation of RASSF1A, p16, and glutathione S-transferase pi gene promoters was quantified by methylation-specific PCR. This study provides an original molecular characterisation of arsenic hepatotoxicity in a high-exposure Nigerian community and develops a novel epigenetic toxicology framework applicable to environmental health policy. Keywords: arsenic, epigenetic disruption, hepatotoxicity, groundwater contamination, Plateau State.