2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induced perturbation of calcium distribution in the rat.

ABSTRACT

Altered calcium homeostasis may play a central role in the liver injury produced by some toxicants. Therefore, the dose and time dependent effects of TCDD on calcium distribution in whole homogenate and subcellular fractions of liver were examined. Groups of female rats were treated with 40 micrograms TCDD/kg for 1, 2 or 3 days. Animals treated with TCDD for 1 and 2 days were killed 1 day after treatment. Rats treated for 3 days were killed on days 1, 3, 5, 7, 9 and 12 post-treatment. A 2-fold increase in calcium content in whole homogenate occurred 5 days post-treatment. Increases in mitochondrial calcium were noted 3 days post-treatment, and significant increases in microsomal calcium were observed one day post-treatment. Small increases in cytosolic calcium also occurred. Thus, TCDD produces disturbances in the content and subcellular distribution of calcium which may contribute to the promotion of toxic manifestations by this xenobiotic.