Primary rat Sertoli and interstitial cells exhibit a differential response to cadmium.

Two cell types central to the support of spermatogenesis, the Sertoli cell and the interstitial (Leydig) cell, were isolated from the same cohort of young male rats and challenged with cadmium chloride to compare their susceptibility to the metal. Both cell types were cultured under similar conditions, and similar biochemical endpoints were chosen to minimize experimental variability. These endpoints include the uptake of 109Cd, reduction of the vital tetrazolium dye MTT, incorporation of 3H-leucine, change in heat-stable cadmium binding capacity, and production of lactate. Using these parameters, it was observed that the Sertoli cell cultures were adversely affected in a dose-and time-dependent manner, while the interstitial cell cultures, treated with identical concentrations of CdCl2, were less affected. The 72-hr LC50's for Sertoli cells and interstitial cells were 4.1 and 19.6 microM CdCl2, respectively. Thus, different cell populations within the same tissue may differ markedly in susceptibility to a toxicant. These in vitro data suggest that the Sertoli cell, in relation to the interstitium, is particularly sensitive to cadmium. Because the Sertoli cell provides functional support for the seminiferous epithelium, the differential sensitivity of this cell type may, in part, explain cadmium-induced testicular dysfunction, particularly at doses that leave the vascular epithelium intact.

Toxic effects of ophthalmic preservatives on cultured rabbit corneal epithelium.

We investigated the effects of the ophthalmic preservatives thimerosal and sorbic acid on the proliferation and survival of rabbit corneal epithelial cells in tissue culture. Normally, explants of corneal epithelium grow vigorously during the first 7 days in culture. With 0.004% thimerosal present in the culture medium, the normal proliferation of corneal cells is suppressed completely. When 0.1% sorbic acid is present, proliferation is delayed and the lifespan of the corneal cells is reduced. After a 1-h exposure to concentrations of thimerosal of 0.0005% or greater, virtually all corneal cells present in established cultures are killed. These results suggest that use of ophthalmic preparations containing these chemicals may affect the metabolic and proliferative capacity of the corneal epithelium adversely.

Qualitative and quantitative aspects of human fetal liver metallothioneins.

This study examined the status of zinc, copper, and metallothionein (MT) in 31 second trimester (13-23 weeks) human fetal livers. In addition, the metal-binding capacities of concomitant and term placentas were investigated in the light of the role of this organ in transport and binding of the potentially toxic group IIb elements, notably cadmium and mercury. Qualitative analyses indicate that human fetal liver contains three "isoforms" of MT, with the second form (MT-1) being predominant. DEAE A-25 anion exchange chromatography revealed that human fetal hepatic MT-1 and MT-2 elute similarly to native newborn and cadmium-induced adult rat liver MT, MT-1 and MT-2. A significant quantity of a third isoform, which eluted in low-ionic-strength buffer, is also present in human fetal liver. The function of this isoform may be developmental in nature. Quantitative analyses show that MT levels are high (approximately 6.4% of the soluble protein) and correlate well with zinc in human fetal hepatic cytosol. In contrast, copper levels were low, and no significant correlation could be seen with MT. A slight, but significant positive correlation existed between gestational age (in weeks) versus zinc and MT levels (tissue weight basis); after normalizing for protein, no relationship could be observed. Both preterm and term placenta showed low levels of zinc and MT. It is suggested that the low level of cadmium-binding capacity seen in placenta may be one factor in the susceptibility of this organ to cadmium.