Energy Balance, Organochlorine Exposure, and Possible Toxicologic Effects

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DESCRIPTION (provided by applicant): Polychlorinated biphenyls (PCBs) have been implicated as potential carcinogens, particularly in studies of non- Hodgkin's lymphoma. PCBs remain a public health concern despite ceasing production, because of bioaccumulation in the food chain and their presence in adipose tissue of virtually every person. PCBs and other organochlorines find a stable reservoir in fat; however, they are excreted to the bloodstream with lipid mobilization during times of negative energy balance, such as weight loss. This process of organochlorine mobilization exposes cells and tissues to increased concentrations of PCBs, thereby creating a window for enhanced toxicologic effects. Aims of this study are to investigate associations between exercise-induced weight loss, PCB concentrations, and immune function among postmenopausal women. The proposed study builds on resources from an existing randomized controlled trial of exercise with an extensive assessment of immune function biomarkers. Subjects are postmenopausal women (Seattle, USA) who participated in a one- year randomized trial to study biologic effects of exercise. In the proposed study, we will measure PCB concentrations in plasma samples from 100 subjects (50 intervention arm, 50 controls) both prior to the intervention and at a 12-month follow-up visit. Data on PCB concentrations and existing trial data will be used to: 1) Evaluate relationships between energy balance characteristics and plasma PCBs, both prior to the intervention and across the trial period; and 2) Investigate immune effects of PCB exposure, both prior to the intervention and following any changes in PCB concentrations that result from the exercise intervention. We will explore how circulating PCB concentrations are associated with specific aspects of energy balance such as weight and weight cycling history, body composition including abdominal adiposity, and changes in weight and body composition during the intervention. Additionally, the study design will allow investigation of how PCB 'dose' resulting from weight loss during the trial affects immune function measures such as lymphocyte phenotypes, natural killer cell cytotoxicity, and lymphocyte proliferation. We hypothesize that the exercise intervention will be associated with increases in plasma PCB concentrations, and that PCB increases will be most pronounced among women with the greatest body fat loss. Furthermore, we hypothesize that increases in PCBs during the trial will be correlated with decreased lymphocyte proliferation and other markers of immune function. The proposed study represents a unique opportunity to expand the state of knowledge about energy balance, organochlorine exposure, and possible toxicologic effects by studying these relationships in a population-based sample of healthy women, within an existing framework of a randomized trial with rich data resources. The proposed project will describe associations of changes in weight and/or body composition with organochlorine exposure, and will investigate immune effects of polychlorinated biphenyl (PCB) exposure before and after weight loss. The study has significant relevance to public health because of both the growing problems of obesity and weight cycling in the United States and the ubiquitousness of PCB pollution. Understanding possible toxicologic effects of organochlorine exposure following weight loss may provide clues about certain detrimental effects of energy imbalance.