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

Abstract

A bovine kidney cell culture system was used to assess what relationship mercuric chloride (HgCl ₂ ) uptake and subcellular distribution had to cytotoxicity. Twenty‐four‐hour incubations with 0.05–50 μM HgCl ₂ elicited a concentration‐related cytotoxicity. Cellular accumulation of ²⁰³ Hg was also concentration‐related, with 1.0 nmol/10 ⁶ cells at the IC50. 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). However, the subcellular distribution of Hg was not concentration‐related. Mitochondria and soluble protein fractions accounted for greater than 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.