CYTOTOXICITY, ZINC PROTECTION, AND STRESS PROTEIN INDUCTION IN RAT PROXIMAL TUBULE CELLS EXPOSED TO CADMIUM CHLORIDE IN PRIMARY-CELL CULTURE

Primary cell culture was utilized to study the relationships between s tress protein induction by zinc in vivo and cadmium toxicity in vitro. Effects of cadmium on cell viability were evaluated by the alamar blu e assay, in conjunction with the ultrastructural morphology of cells b y transmission electron microscopy. The expression of stress protein g ene products was evaluated by S-35 two-dimensional gel electrophoresis . The results showed cytotoxicity of CdCl2 at and above 129 mu M (14.5 5 mu g cadmium/mL medium) following 4 h of exposure. Prior zinc admini stration (20 mg zinc/kg, s.c., two daily doses) in vivo significantly protected the cells in vitro as demonstrated by improved cell viabilit y. The S-35 labeling of proteins induced by CdCl2 exposure clearly dem onstrated for the first time that gene product of the 70-kDa family wa s induced in cultured rat proximal tubule cells which are the target c ells for cadmium toxicity in vivo. Zinc in vivo pretreatment of animal s induced proteins in the 90-, 70-, and 38-kDa families, which may act together with metallothionein to protect cells against cadmium toxici ty. The results also indicate that the protective effect of zinc remai ns after the cells have been put in culture and thus provides a system in which we can study the changes that occur as a result of zinc expo sure that decreases cadmium toxicity.