A new combined quantitative cytophotometric method for estimating sulphydryl groups or disulphide bonds, and total protein in liver sections; applied to rats chronically exposed to cadmium.

A detailed procedure is described for a new combined quantitative cytophotometric method for estimating sulphydryl groups or (and) disulphide bonds as well as total protein. When applied to livers of cadmium treated rats and appropriate controls a dose response effect was demonstrated for the quantity disulphide bonds per unit protein.

Large increase in disulphide bonds containing cytosol proteins after chronic cadmium administration, estimated in isolated rat liver cells.

Using histochemical staining, followed by cytophotometric quantitation of disulphide bonds and total protein in isolated liver cells of rats treated for a long time with low doses of CdCl2, a large increase in disulphide bonds containing proteins could be demonstrated in cells of one ploidy class. This increase seems to be due to an increase in high molecular weight (HMW) cytosol proteins as estimated biochemically. They probably represent polymers of metallothionein.

Histochemical changes in protein disulphide bonds in rat liver and kidney after chronic cadmium administration, and the possible relation to metallothionein.

After chronic exposure to low doses of CdCl2 an increase in disulphide bonds has been established in rat liver using a specific staining method for disulphide bonds and cytophotometric quantitation. This increase is dependent on doses and length of exposure time. Evidence is presented that this increase might be related to the accumulation of metallothionein or some other cadmium binding protein. Using the same staining method after long exposure to low doses of CdCl2 a large number of large dark blue stained granules were observed in the proximal tubule cells, with blue stained deposits in the lumen of the proximal and some renal medulla tubules of the kidney. Evidence is presented that this staining pattern corresponds to the destruction of the proximal tubule cell by the cadmium thionein complex.

Investigation of the mechanism of cadmium toxicity at cellular level. I. A light microscopical study.

Chromatin condensation occurs within 15 min to 1 h after the addition of CdCl2 in a concentration of 1 microgram/ml to a liver cell culture and seems to be the first event demonstrable by light microscopy. This chromatin condensation, which precedes membrane leakage, is irreversible and leads to cell death of almost all cells. It does not occur after the administration of equimolecular concentrations of some other bivalent metallic ions.

The effect of a single sublethal administration of cadmium chloride on the microcirculation in the uterus of the rat.

A light microscopical and ultrastructural survey of the early effects of cadmium chloride in the uterus of the prepubertal rat was performed. 3 h after injection of CdCl2 evidence of injury to the microcirculation was ultrastructurally apparent. The phenomena consisted of nuclear and nucleolar changes, extensive pinocytotic activity, vacuolisation of the cytoplasmic matrix, distension of the cisternae of the endoplasmic reticulum and an increase in cytoplasmic protrusions in the lumen of the cell. After 6 h the damage had increased and a certain portion of the endothelial cells showed signs of degeneration. At 24 h the changes were maximal and extruded red cells were observed in the interstitial tissue by light microscopy. At 48 h recovery had started and the situation appeared to return to normal.