Human Health TDC

Persistent organic pollution is a global problem. This fact is especially apparent in the Arctic where pesticides currently used in distant environments accumulate, in some cases to higher levels than those observed in the source region. This pollution threatens the well-being of the aboriginal inhabitants of these regions. Most of the traditionally harvested animals in the Arctic are long-lived and from the higher trophic levels of the food chain, thereby providing an opportunity for considerable bioaccumulation and biomagnification of persistent contaminants. This has prompted a growing concern by the Alaska Inupiat that pollutants in the environment might be contributing to their unique morbidity and mortality rates, especially of their children. Our studies are currently focused on two specific organic pollutants found in the Arctic environment; 1}hexachlorobenzene (HCB), a byproduct during manufacture of several different chlorinated compounds and consistently detected in the Arctic and, 2} dichlorodiphenyl dichloroethylene (p,p’-DDE), a chlorinated environmental breakdown product measured in the Arctic population at significantly higher concentrations than the parent pesticide, DDT. We hypothesize that mammalian embryonic cell exposure to these chemicals, individually or as mixtures at environmentally relevant concentrations and ratios, will alter the cell cycle and/or cause death by apoptosis, rather than by necrosis. We also predict synergistic cytotoxicity of the chemical mixture because of an accumulation of deleterious effects at different cellular target sites by each chemical. We further hypothesize that while some chemicals target non-genetic cellular components (such as a cell membrane or cytosolic component), other chemical effects will occur primarily at the genetic level, directly or indirectly. Our experiments have been designed as a set of sensitive cellular and molecular assays to compare levels and types of cytotoxic and genotoxic activity of the above chemicals (individual and mixture), at environmentally relevant concentrations, upon embryonic cells in culture. Our experimental evidence thus far is that these chemicals, separately or as a mixture at concentrations and molar ratios relevant to that measured in the Arctic environment, do have cytotoxic and/or genotoxic effects that could result in profound consequences to exposed tissues of a developing embryo or fetus. We have further experimental evidence that exposure to both chemicals at environmentally relevant concentrations is more toxic to the cell than the sum of effects by exposure to the individual chemicals. Experimental results indicate this is due to different cellular target sites for each chemical (Appendix A: Preliminary Results).