ACUTE TOXICITY EFFECTS OF MERCURY AND OTHER HEAVY-METALS ON HELA-CELLS AND HUMAN-LYMPHOCYTES EVALUATED VIA MICROCALORIMETRY

We have developed a microcalorimetric bioassay for acute toxicity based on heat evolution from intact cells. A reduction in heat production by cells reflects the inhibition of various biochemical reactions which constitute the cell's metabolic processes. For ten toxicants, including the heavy metals Hg, Cd, Cu, Pb, Cr, V, and As, we have measured the concentrations that are 50% effective (EC50) in inhibiting heat evolution in tissue-cultured HeLa cells and in human peripheral blood lymphocytes. These data are compared with results of other acute toxicity tests and with microcalorimetric studies of heat evolution in the chemiluminescent bacterium Photobacterium phosphoreum. This comparison indicates that heat production may be the optimum measure of cellular metabolism for instrumental toxicological purposes since it reflects the sum of cellular metabolic processes and since it detects diffferential sensitivities of various cell types to toxicants. We have further studied effects of one heavy metal, mercury, on cell plasma membrane proteins using fluorescence photobleaching recovery (FPR) methods. Mercury induces formation of large membrane protein aggregates which disrupt cell function. FPR results suggest that, even at very low Hg concentrations, small aggregates form rapidly and increase in size causing, within one hour, measureable reductions in protein lateral diffusion. © 1990.