CYTOTOXIC EFFECTS OF AROCLOR-1254 ON ULTRASTRUCTURE AND BIOCHEMICAL PARAMETERS IN CULTURED FETAL-RAT HEPATOCYTES

The cytotoxicity of a commercial PCB mixture, Aroclor 1254, was assess ed on cultured foetal rat hepatocytes. Under control conditions, dexam ethasone stimulates immature hepatocytes to differentiate into both he patocytes and biliary epithelial cells. Consequently, foetal rat hepat ocytes maintain, in vitro, a liver-like organization with spaces corre sponding to the lumen of biliary canalicules, many mitochondria, and a well-developed rough endoplasmic reticulum (RER). This in vivo-like o rganization of cultured rat hepatocytes remains unchanged in medium su pplemented with Aroclor 1254 at concentrations below 25 mu M. In the 2 5-125 mu M concentration range, however, PCBs severely alter some cell ular organelles, notably causing important development of the RER and the appearance of cytoplasmic lacunae containing laminated concentric membrane arrays. In. addition, the number of lipid droplets increases, the glycogen islets disappear, and dramatic local alterations of the mitochondrial cristae occur. In exposed and unexposed cells, the follo wing biochemical parameters were measured: the DNA content, protein sy nthesis, lipid peroxidation, and urea formation. The results show that Aroclor 1254 at concentrations exceeding 25 mu M (but not at lower co ncentrations) causes irreversible damage to cultured hepatocytes. The observed ultrastructural modifications are in good agreement with seve ral in vivo studies on rat liver, Thus, isolated foetal rat hepatocyte s have considerable potential as an alternative to whole animals for u se in (eco)toxicological studies.