The role of lysosomes in the pathogenesis of copper-induced hepatotoxicity. II. Intracellular distribution of copper in hepatocytes.

The effects of altered lysosomal function on the pathogenesis of copper-induced hepatotoxicity were studied in C57B1/6 bg/bg (beige) and C57B1/6 bg/+ (conventional) mice. Copper loading was accomplished through daily ip injections of aqueous copper chloride at a dosage rate of 8 mg/kg body weight for 1, 2, and 4 weeks. The subcellular distribution of copper in copper-treated beige mice was significantly different than that in conventional mice. Beige mice had consistently higher levels of copper in the nuclear and cytosolic fractions with lower levels in the heavy and light mitochondrial fractions. The copper levels were lowest in the microsomal fractions of both groups of copper-treated mice and remained similar throughout the 4-week experiment. Levels of total hepatic copper were similar in both groups of mice receiving parenteral copper except at Day 14, when beige mice had higher levels.