Biochemical Toxicology of Polycyclic Aromatic Hydrocarbons from Smoked Fish Consumed in the Niger Delta: Metabolite Biomarkers and Cancer Risk Assessment

Smoked fish is a dietary staple consumed across the Niger Delta region, and the polycyclic aromatic hydrocarbon contamination generated during smoking processes represents a potentially significant carcinogenic exposure that has not been systematically characterised from a biochemical toxicology perspective. This dissertation investigates the biochemical toxicology of polycyclic aromatic hydrocarbons from smoked fish consumed in the Niger Delta, characterising metabolite biomarkers in exposed populations and constructing an original cancer risk assessment framework. Polycyclic aromatic hydrocarbon contamination was determined in twenty-five commonly smoked fish species collected from markets in Rivers, Delta, and Bayelsa states by GC-MS following solvent extraction and solid-phase clean-up. Urinary 1-hydroxypyrene and 3-hydroxybenzo[a]pyrene as biomarkers of pyrene and benzo[a]pyrene exposure respectively were quantified by HPLC-fluorescence in three hundred smoked fish consumers and one hundred non-consumer controls from the same communities. Cytogenetic damage assessment by micronucleus frequency in buccal cells provided a genotoxicity endpoint. DNA adduct formation in lymphocyte DNA was assessed by the 32P-postlabelling method in a sub-group of twenty high-exposure consumers. CYP1A1 and CYP1B1 genetic polymorphisms modifying bioactivation of benzo[a]pyrene were genotyped. Smoked fish samples showed benzo[a]pyrene concentrations above the EU maximum limit in 64 percent of samples. Urinary biomarker levels were significantly elevated in consumers and correlated with smoked fish consumption frequency. DNA adducts and elevated micronucleus frequency confirmed genotoxic exposure in high consumers. CYP1A1 Ile462Val polymorphism was associated with significantly higher DNA adduct burden at equivalent exposures. An original probabilistic cancer risk assessment framework integrating biomarker, dietary, and genetic data was developed. Keywords: polycyclic aromatic hydrocarbons, smoked fish, cancer risk, DNA adducts, Niger Delta.