Regional Expression of Heat Shock Protein-72 (hsp72) Induced in Rat Liver by the Hepatotoxicant Cadmium (CdCl2)
P.L. Goering1, R.R. Dugyala1, B.R. Fisher2 and R.J. Marler2, 1CDRH, FDA, Rockville, MD, 2Covance Laboratories, Vienna, VA
Many toxic agents enhance the expression of hsps, a cellular response that may be a useful biomarker of toxicity in pre-clinical test batteries. CdCl2 is lab tool we use that is known to produce necrosis across the liver. Determining the cell-specific localization of markers such as hsp72 will allow us to understand their roles in cell injury. Rats received single, sub-necrotic, iv dosages of CdCl2. No treatment-related histopathological changes were observed. No immunostaining signal specific for hsp72 was observed in untreated controls. The most intense signal was observed 16 hr after exposure to 2 mg Cd/kg. Hsp72 accumulation was predominantly localized in the cytoplasm of centrolobular hepatocytes, primarily around venules. These results demonstrated that hsp72 expression in response to acute Cd exposure occurs in hepatocytes located in centrolobular areas and adjacent to larger intrahepatic venules prior to the onset of overt cytotoxicity.