ENHANCED RENAL TOXICITY BY INORGANIC MERCURY IN METALLOTHIONEIN-NULL MICE

To elucidate a protective role of metallothionein (MT) in the manifest ation of inorganic mercury toxicity, we studied the susceptibility of MT-null mice to the renal toxicity of mercuric chloride. Because the M T-null (J) mice are a genetic background of 129/Sv strain, the 129/Sv mice were used as wildtype controls. Nine-week-old male MT-null (J) an d 129/Sv mice were given subcutaneous injections of mercuric chloride at doses of 10 to 40 mu mol/kg. The basal MT level in the kidney of MT -null (J) mice was undetectable (<0.2 mu g/g of tissue) and similar to 2.5 mu g/g of tissue in 129/Sv mice. The sensitivity to the renal tox icity of mercuric chloride was markedly enhanced in the MT-null (J) mi ce compared with the 129/Sv mice. The renal mercury level was similar for the MT-null (J) and 129/Sv mice at 4 hr after the injection of mer curic chloride (20 mu mol/kg) but became significantly lower in MT-nul l (J) mice than in 129/Sv mice at 24 and 72 hr. Based on the present r esults, we conclude that MT is an important protective factor against the renal toxicity caused by inorganic mercury and that it may play a major role in the retention of mercury in the kidney.