Insufficient metallothionein synthesis in the lung and kidney in human acute inorganic mercury poisoning

Abstract

It has been assumed that 'smelter disease' is caused by sulfuric dioxide. A typical episode resulting in 'smelter disease' occurred in Fukushima, Japan. Twenty-seven workers became ill and eventually three of them died. The concentration of mercury (Hg) was found to be higher in all tissues and blood of the three victims than in those of normal Japanese, although the concentrations of zinc, cadmium, copper and lead in all tissues examined were within the normal range. The clinical course after the incident and autopsy findings clarified the cause of death to be acute Hg fume poisoning. To determine the histological localization of Hg and metallothionein (MT), Hg staining by the photo-emulsion method and immunostaining using anti-MT antibody were carried out. Numerous Hg granules were observed in the epithelia of the proximal tubules of the renal cortex using the photo-emulsion histochemical method. The liver of victims contained a few Hg granules in the hepatic cellular cytoplasm and sinusoid. Immunostaining of the kidney showed a strong positive reaction with anti-MT in the proximal tubules outside the medulla. The presence of Hg-bound MT in the kidneys of the victims was confirmed by gel chromatography. This is the first evidence of Hg-MT in the tissues of humans with acute Hg fume poisoning. Mercury might induce the synthesis of MT in human tissues. In addition, fractionation of the supernatants on gel chromatography revealed that most of the Hg in the kidney and lung of the patient who had the most severe renal and lung damage and who was the first of the three victims to die was distributed in high molecular weight protein fractions (HMW) and a small portion of Hg was bound to MT. These findings suggest that the amount of synthesized MT in tissues was not sufficient for MT to bind to Hg. The amount of Hg absorbed into tissues may be too large for MT to protect tissues, and thereby Hg may be bound to HMW.