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We have investigated gross pathology, physiological (steroid precursors) and toxicological responses (oxidative stress and phase II biotransformation) in relation to tissue contaminant burden in Tilapia species along the entire length (320 km) of Ogun River, Nigeria. The Ogun River is the longest and largest river in Southwestern Nigeria located along heavily industrialized cities and receives complex mixtures of effluents. A total of 1074 tilapias were collected from three sampling points (Abeokuta, Isheri and Ikorodu) and from an upstream control point (Igboho) and evaluated for gross pathological changes, hepatic transcript levels for oxidative stress and phase II biotransformation responses. Trace metal concentrations and POPs in muscle samples were analyzed using ICP-MS and GC-MS respectively. Evaluation of gross pathological changes showed a 50-, 33-, 17 and 0% prevalence of hepatic tumors at the Ikorodu, Abeokuta, Isheri and Igboho sites, respectively. Plasma concentrations of cholesterol and pregnenolone showed apparent significant decreases at downstream sites of the control point in both male and female fish (except for pregnenolone levels of male fish at Ikorodu). Inversely, gst, ugt -1, ZuCu-sod and sod significantly increased in fish collected from downstream sites, compared with the control site and these increases paralleled the significant increase in trace metal and POPs concentrations at these sites. PCA revealed a site related association between measured toxicological responses and contaminant burden, indicating a potential cause-and-effect relationship. Thus, the possible adaptation of Ogun River Tilapia species to contaminants may have significant consequences on cellular, physiological and biochemical processes regulating metabolism, growth, development and reproduction, and also have serious human health consequences, since the Ogun River is used for fisheries and domestic water supply for surrounding neighborhoods. [ABSTRACT FROM AUTHOR]