Cellular distribution of inorganic mercury and its relation to cytotoxicity in bovine kidney cell cultures

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Abstract
A bovine kidney cell culture system was used to assess what relationship HgCl2 uptake and subcellular distribution had to cytotoxicity. Incubations (24 h) with 0.05-50 .mu.M HgCl2 elicited a concentration-related cytotoxicity. Cellular accumulation of 203Hg was also concentration-related, with 1.0 nmol/106 cells at the IC50 [median inhibitory concentration]. Measurement of Hg uptake over the 24 h exposure period revealed a multiphasic process. Peak accumulation was attained by 1 h and was followed by extrusion and plateauing of intracellular Hg levels. Least-squares regression analysis of the cytotoxicity and cellular uptake data indicated a potential relationship between the Hg uptake and cytotoxicity (r = 0.91). The subcellular distribution of Hg was not concentration-related. Mitochondria and soluble protein fractions accounted for > 65% of the cell-associated Hg at all concentrations. The remaining Hg was distributed between the microsomal (6-10%) and nuclear and cell debris (11-22%) fractions at all concentrations tested. Less than 20% of the total cell-associated Hg was bound with metallothionein-like protein.