The genotoxicity and cytotoxicity of dermally-administered cadmium: effects of dermal cadmium administration.

Cadmium, unlike zinc, selenium and copper, has no known biological importance, and therefore, it is classified as a carcinogen in humans, as well as in animals. The effect(s) of levels of dermally-administered cadmium on cadmium genotoxicity and cytotoxicity was investigated in Harlan Sprague-Dawley rats for 14, 21, 28, 35 and 42 days at concentrations of 14 and 28 mg/kg/day. Exposure of rats to cadmium via dermal application caused lesions on the skin (hyperkeratosis, acanthosis and scabbing, alopecia and erythema) and tumors in the scrotum. Anatomical changes, such as distention of the stomach, atrophy of kidney and liver and loss of body weight were also observed in these rats. The toxic effects of cadmium on cell ultrastructure were nuclear membrane damage, chromatin condensation, regression of mitochondrial cristae and ultimately cell death. Analyses of the brain, kidney and liver cells of rats exposed to cadmium, clearly showed DNA damage. Of the three organs examined, DNA from kidney cells sustained the most damage followed by DNA in liver cells. There is a positive correlation between Cd dose(s) and duration of exposure and the extent of DNA damage.

Comparative studies of in vivo genotoxic effects of cadmium chloride in rat brain, kidney and liver cells.

Cadmium chloride-induced DNA damage was investigated in individual brain, kidney and liver cells isolated from rats gavaged 14 mg/kg/day cadmium chloride. Animals were sacrificed on days 2, 4, 8, 16, and 33, and DNA damage was determined using the recently developed alkaline microgel electrophoresis technique. Data for DNA migration from 50 randomly selected cells clearly show significant increases in DNA damage in cells from three different organs of cadmium chloride gavaged animals compared to saline treated control animals (33 day control, brain 64.7 +/- 5.3, kidney 75.5 +/- 9.4, liver 67.9 +/- 5.7 microm; 33 days experimental, brain 284.3 +/- 16.9, kidney 397.9 +/- 11.3, liver 315 +/- 22.5 microm; these values represent length of exposure in days and length of DNA migration in micron). There was an increase in DNA damage for all three cell types, with increasing duration of treatment. Cadmium (CdCl2) induced levels of DNA single strand breaks were more pronounced in kidney cells than in cells from the other two organs. Body and organ weights decreased of treated animals were decreased as compared to control. Results of this study indicate a potential of cadmium to be a genotoxic compound.

Schistosoma mansoni miracidial behavior: an assay system for chemostimulation.

A new system for evaluating the responses of miracidia to chemostimulants is described. The apparatus consists of a translucent plastic block with a center well and a hole in the edge leading to the well. One end of a glass tube, covered with a dialysis membrane, was inserted into the hole. Experimental solutions to be tested were put into the tube and Schistosoma mansoni miracidial behavior was observed in the well on the other side of the permeable membrane. Miracidia were released near the membrane; those which contacted the membrane were scored as to whether they returned (contact with return) or did not return (contact without return) before leaving the field of view. Materials eliciting significantly more contact with return responses than did controls were considered to be stimulatory. In this assay system, snail (Biomphalaria glabrata) conditioned water elicited 75% contact with return as compared to 8% for well water control (P less than 0.05). Tracings from motion pictures showed swimming behavior of miracidia toward snail-conditioned water to be different from behavior toward well water controls. This system permits generation of dilution response curves for chemicals and provides generally quantitative results.