CIRCULATING LYSOZYME AND HEPATIC CYP1A ACTIVITIES DURING A CHRONIC DIETARY EXPOSURE TO TRIBUTYLTIN (TBT) AND 3,3',4,4',5-PENTACHLOROBIPHENYL (PCB-126) MIXTURES IN CHANNEL CATFISH, ICTALURUS PUNCTATUS

Abstract

Exposure to planar congeners of halogenated aromatic hydrocarbons (HAHs) leads to a myriad of toxicities, including developmental, reproductive, and immunotoxic effects. Halogenated aromatic hydrocarbons possessing structural similarity to TCDD, such as 3,3',4,4',5-pentachlorobiphenyl (PCB-126), are more prevalent in the environment than TCDD, and they elicit similar toxic effects, primarily through the cytosolic aromatic hydrocarbon receptor (AhR). While polychlorinated biphenyls (PCBs) are ubiquitous pollutants, they rarely exist alone in the environment. The aquatic biocide tributyltin (TBT) is also a widespread environmental contaminant, and numerous studies indicate that it has reproductive, developmental, and immunotoxic effects in a variety of organisms. Unlike planar HAHs, TBT is not associated with any known cellular receptor. The induction of cytochrome P-4501A (CYP1A) activity in most vertebrates is a classical physiological response to planar HAH exposure. TBT has been shown to inhibit the induction of cytochrome P-450s at high doses. Recent studies demonstrate that low levels of TBT potentiate PCB-126-associated CYP1A induction in channel catfish, Ictalurus punctatus , and in rodents following intraperitoneal injections. In this study, the effects of dietary exposures to TBT, PCB-126, and mixtures of the two on channel catfish hepatic CYP1A activity, as well as plasma lysozyme activity, were examined. Circulating lysozyme, a marker of proinflammatory responses, was monitored to determine the relative specificity of treatments for CYP1A induction. Plasma lysozyme levels were examined along with hepatic CYP1A protein induction and EROD activity following exposure to nominal doses of 1 and 100 ppb dietary TBT, PCB-126, or mixtures of the two. As expected, the highest level of PCB-126 induced CYP1A, and TBT did not. In mixtures, the low level of TBT potentiated the ability of the high PCB-126 dose to induce CYP1A. Plasma lysozyme levels were suppressed by both concentrations of TBT and by the low concentrations of PCB-126 during the initial phase of the response to Vibrio anguillarum . The normal and expected pattern of initial increases in circulating lysozyme levels following immunization, with subsequent return to baseline level, was disrupted by TBT. High levels of PCB-126 potentiated the lysozyme response. As seen with CYP1A activities, exposures to mixtures of TBT and PCB-126 resulted in a potentiation of plasma lysozyme levels. The data show that dietary TBT modulates PCB-126-induced CYP1A activities and that these mixtures may have potent proinflammatory properties as well.