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In summary lower selenium concentrations were found in the lung cancer group compared to other smelter workers and controls. The two lowest selenium values in the total material were found in two of the lung cancer workers. This is in agreement with earlier reports of lower blood selenium levels in cancer patients (Willett et al 1983, Salonen et al 1984). An increased cancer incidence has also been found in geographical areas with low selenium contents in forage crops (Shamberger et al 1976). Numerous animal experiments have demonstrated an anticarcinogenic effect of selenium. Our conclusion is that selenium might have a protective effect in occupational exposure against at least certain carcinogens causing lung cancer. Looking at the dominant worksites the workers have obviously been exposed to different concentrations of selenium over the years. As selenium has not been particularly under observation, few dust analyses are available, and so the dust load in exposed workers cannot be directly calculated. The excretion rates show individual differences. In three of the seven lung cancer cases we noted that, despite a considerable and continuous exposure to selenium in the course of their work, they had low selenium concentrations in their lung tissue at the time of death. Two other workers in the lung cancer group had also been working at worksites with considerable exposure to selenium. Raised cadmium levels were noted in the lung cancer group.(ABSTRACT TRUNCATED AT 250 WORDS)

Epithelial cells from the kidney were freshly isolated from rats pretreated by daily subcutaneous doses of CdCl2 in vivo (0.5-2 mg Cd/kg X 5). Such cells were incubated in vitro in media with different concentrations of cadmium chloride (0-200 micrograms Cd/ml). There was no inhibition of cell growth in such cells. However, in cells isolated from non-treated rats, in vitro exposure to the same concentrations of CdCl2 caused a dose dependent decrease in viability. When cells, isolated from non-treated rats were pretreated in vitro with CdCl2 (10 micrograms/ml) and subsequently exposed to cadmium chloride (0-200 micrograms/ml), a protective effect was observed, which was similar to the one observed in cells isolated from animals pretreated with CdCl2. The concentration of metallothionein in the cells treated with cadmium was increased. A lower uptake of cadmium chloride, in vitro has been observed in kidney cells pretreated in vivo or in vitro compared to nonpretreated cells. Subcellular distribution studies indicate that Cd-distribution was similar in pretreated and non-pretreated cells, but concentrations were generally lower in the pretreated cells. The decreased uptake of Cd by pretreated kidney cells is a sign of Cd-interference with cellular function. These changes are suggested as a contributing mechanism to the prevention of acute toxic effects of cadmium on the kidney.

Chelating agents like NTA (nitrilotriacetic acid) STPP (sodiumtripolyphosphate, Na5P3O10) and EDTA (ethylenediaminetetraacetic acid) are used as components of detergents. An increased toxicity of some metal compounds when combined with NTA has led to decreased use of this chelating agent in relation to STPP. In the present studies short-term and long-term effects of these chelating agents on cadmium toxicity in mice were investigated. I: In the short-term study, mice subcutaneously exposed to CdCl2 (3.2 mg Cd/kg b. wt.) in combination with STPP (32 mg/kg b. wt.) demonstrated a markedly higher mortality compared to animals given CdCl2 alone. This increase in mortality was similar to the one encountered when CdCl2 (3.2 mg Cd/kg b. wt.) and NTA (32 mg/kg b. wt.) were combined. Animals exposed subcutaneously to CdCl2 + STPP or CdCl2 + NTA showed histological evidence of liver necrosis 24 hrs after exposure not seen in animals given the same dose of CdCl2 alone and also had markedly lower cadmium concentrations in the livers compared to only Cd-exposed animals. II: In the long-term study, mice were exposed orally to CdSO4 (50p.p.m Cd) alone or in combination with STPP (500 p.p.m.), NTA (500 p.p.m.) or EDTA (50 p.p.m.) by continuous administration via the drinking water for 18 months. A decreased total excretion of urine proteins was seen in all Cd-treated animals irrespectively of the combination with various chelating agents. The conclusion of the present work was the NTA and STPP given by subcutaneous injection to mice markedly increased the toxicity of cadmium but that neither NTA, STPP nor EDTA given orally altered the toxicity of cadmium during a period of long-term exposure of 18 months.

Liver proteins from mice injected subcutaneously with cadmium chloride (3 mg Cd/kg body weight) were separated on G-75 Sephadex at intervals 20 min.-21 days after injection. Fairly soon after the injection, cadmium was found bound to proteins of high molecular weight whereas at survival times exceeding 24 hours the cadmium was associated with a low molecular weight protein. In mice repeatedly exposed to cadmium (0.25 mg/kg, daily, 5 days/week) for periods up to 5 months, cadmium was principally bound to the low molecular weight protein, which has characteristics in common with the earlier described protein, metallothionein. The importance of “mouse metallothionein” in the toxicity of cadmium is discussed.

The influence of age, pretreatment with CdCl2 and long-term oral treatment with CdSO4 on whole-body retention, organ distribution and the biological half-time of 109CdCl2 (given as a single oral dose) was studied in mice in three separate experiments: I) Male CBA-mice, 1, 3 and 6 months of age, were given a single oral dose of CdCl2 labelled with 109Cd. The whole-body retention of the radiolabelled cadmium was inversely related to age. This was explained by a significantly higher intestinal absorption of 109Cd in the younger mice, compared to the older. No influence of age on the biological half-time of 109Cd was observed. II) Three groups of adult of male CBA-mice were pretreated with 75 mgCd/l (as CdCl2) in the drinking water for 130, 13 or 0 days, respectively, before receiving a single oral dose of CdCl2 labelled with 109Cd. The two pretreated groups showed higher intestinal absorption of radio-labelled cadmium and a statistically significant longer biological half-time of 109Cd compared to mice not pretreated with cadmium. The organ retention of radiolabelled cadmium was markedly higher in mice given cadmium in the drinking water compared with those given deionized water. III) Male and female adult CBA-mice were exposed to a single oral dose of CdCl2 labelled with 109Cd, via stomachtube. and were thereafter given either deionized water (control group) or 50 mgCd/l (as CdCO4) in the drinking water continuously for 18 months. The organ retention of the radiolabelled cadmium was higher in mice exposed to cadmium in the drinking water compared to those given deionized water. Mice exposed to cadmium via the drinking water had a markedly longer biological half-time of 109Cd compared to non-Cd-exposed mice. In all experiments the animals retaining a larger proportion of the cadmium dose showed higher liver: kidney ratios of the radiolabelled cadmium compared to mice retaining less cadmium. The conclusions of the present studies were: Age is of significant importance to the metabolism of cadmium due to the marked raise in intestinal absorption in the youngest age. pretreatment with cadmium caused a higher intestinal absorption of radiolabelled cadmium. A longer biological hall-time of 109Cd was seen both after pretreatment and subsequent treatment with cadmium.