Epigenetic Mechanisms of Occupational Benzene-Induced Hematotoxicity in Nigerian Petroleum Workers: A Molecular Epidemiological Investigation

Benzene-induced hematotoxicity involves complex molecular mechanisms including epigenetic alterations, yet no studies have examined benzene-associated epigenetic changes in Nigerian occupational cohorts. This doctoral molecular epidemiological study investigated epigenetic mechanisms underlying occupational benzene-induced hematotoxicity among petroleum workers in Rivers State, South South Nigeria. A prospective observational cohort design was employed, recruiting 250 exposed downstream petroleum workers and 120 unexposed administrative controls, with biological sampling at baseline, 12 months, and 24 months. Urinary benzene metabolites (S-phenylmercapturic acid, trans,trans-muconic acid), whole blood methylation profiling using Illumina EPIC arrays, LINE-1 global methylation assessment, miRNA expression profiling, and complete blood count analysis were conducted. The study identified significant hypomethylation at benzene metabolism genes including CYP2E1 and CYP1A2 promoter regions in workers with exposures above 1 ppm. Longitudinal analysis demonstrated progressive epigenetic drift in LINE-1 elements with cumulative exposure. miRNA-223 and miRNA-150 were significantly downregulated in workers with concurrent thrombocytopenia, establishing novel mechanistic links. Dose-response relationships between urinary metabolite concentrations and epigenetic alteration magnitude were confirmed. The study presents the first epigenome-wide association study of occupational benzene exposure from a Sub-Saharan African cohort, contributing original molecular evidence to occupational hematotoxicity science. Recommendations include epigenetic biomarker integration into benzene worker surveillance programs and revised occupational exposure limits reflecting low-dose epigenetic effects. Keywords: benzene, epigenetics, hematotoxicity, petroleum workers, molecular epidemiology.