Cadmium toxicity on cultured neonatal rat hepatocytes: biochemical and ultrastructural analyses

The effects of cadmium exposure on the protein secretory functions of cultured neonatal rat hepatocytes were analyzed by both two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and electron microscopy. [35S]Methionine-labelled protein secretion was significantly depressed by cadmium exposure in a dose-dependent manner (1, 10 and 100 microM). Protein secretory patterns resolved by 2D-PAGE and analyzed by autoradiography showed that besides albumin and transferrin, three polypeptide spots decreased their radiolabelling intensities, whereas four spots appeared due to cadmium exposure. Ultrastructural alterations in cultured neonatal rat hepatocytes induced by cadmium exposure were characterized by condensation of the nuclear chromatin, appearance of intra-nuclear inclusions, decrease in number of microvilli, increase in number of intra-mitochondrial granules and transformation of rough endoplasmic reticulum to cytoplasmic vesicles in a dose-dependent manner. Both biochemical and ultrastructural findings indicate that cadmium adversely affects the protein secretory functions of cultured neonatal rat hepatocytes.