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ACCUMULATION OF THE PERSISTENT ENVIRONMENTAL TOXICANTS METHYLMERCURY OR POLYCHLORINATED BIPHENYLS IN IN VITRO MODELS OF RAT NEURONAL TISSUE.
Citation:
Meacham, C A., T. M. Freudenrich, W L. Anderson, L. Sui, S Barone, M. E. Gilbert, W R. Mundy, AND T J. Shafer. ACCUMULATION OF THE PERSISTENT ENVIRONMENTAL TOXICANTS METHYLMERCURY OR POLYCHLORINATED BIPHENYLS IN IN VITRO MODELS OF RAT NEURONAL TISSUE. Presented at Society of Toxicology 42nd Annual Meeting, Salt Lake City, UT, March 9-13, 2003.
Description:
Polychlorinated biphenyls (PCBs) and methylmercury (CH3Hg+) are known toxicants which persist in the environment and accumulate in tissue. Studies to identify mechanisms of action associated with these toxicants have largely been conducted in vitro, and dosimetry comparisons across in vitro preparations and in vivo dosing conditions have not been well defined. The present study examined the accumulation of the PCB mixture Aroclor 1254 (A1254) or CH3Hg+ in commonly used in vitro neuronal models: primary cultures of rat neocortical cells and nerve growth factor differentiated pheochromocytoma (PC12) cells. Cells were exposed to A1254 (0, 3 M) or to CH3Hg+ (0, 10, 100, 1000 nM) in serum-free media for 1 or 24 hr. In addition, cells were exposed to 3 M A1254 in double the media (2x) volume for 1 hr. After each exposure cells were washed, centrifuged, cell pellet weighed, and total PCB or Hg+ content of the tissue was measured by dual column gas chromatography with electron capture detection or by cold vapor atomic absorption, respectively. Neocortical cells exposed to A1254 contained 20.6, 24.1, and 55.4 ppm PCB after 1 hr, 24 hr, and 2x volume respectively. PC12 cells exposed to A1254 contained 66.7, 103.8, and 103.9 ppm for 1 hr, 24 hr, and 2x volume. Neocortical cells exposed to 0, 10, 100, 1000 nM CH3Hg+ contained 0.023, 0.149, 1.206, and 11.498 ppm and 0.032, 0.136, 1.177, and 7.708 ppm after 1 and 24 hr. PC12 cells exposed to CH3Hg+ incorporated 0.128, 0.266, 2.171, 17.473 ppm after 1 hr and 0.086, 0.408, 2.806, 21.855 ppm after 24 hr at 0, 10, 100, and 1000 nM, respectively. These results demonstrate that these neurotoxicants readily accumulate in neuronal tissue in vitro. These results will help to facilitate comparison of in vitro exposures to these compounds with tissue levels observed following in vivo exposure. (This abstract does not necessarily reflect USEPA policy).