Changes in endogenous Zn and Cu distribution in different cytosolic protein fractions in mouse liver after administration of a single sublethal dose of CdCl2

The time course of change in tissue Cd, Cu and Zn contents, their distribut ion in cellular protein fractions as well as the profile of MT gene express ion in mouse liver was described over a 7 days period following a single in traperitoneal injection of 2 mg/kg of CdCl2. The result showed that Cd accu mulated rapidly in mouse liver. Between 1 h and 7 days after administration , over 18% of the total Cd administered were found in the liver. Cd adminis tration was also associated with the overexpression of the MT-mRNA. However , the time course of induction was not parallel to the change in tissue Cd content. When separated on a Sephadex G-75 column, majority of Cd was found to bind to the fractions known to contain the metal-binding protein, metal lothionein (MT). From day 2 after Cd administration, a small amount of the metal was also found associated with the high molecular weight (HMW) protei ns. In addition to Cd, tissue Zn content was affected most during the entir e study. There was a significant decrease in tissue Zn content during the i nitial 8 h but tissue Zn content increased significantly throughout the fol lowing 6 days. At 1-7 days, majority of Zn was associated with the HMW prot ein fraction. Although there was no significant change in total tissue Cu c ontent, distribution of Cu in different protein fractions was detected. Whi le in control animals, Cu was mainly associated with the HMW proteins, some was found in the MT fraction on the second day. On the 7th day, Cu distrib ution had deteriorated. Together with changes seen in Cd: the results might suggest that injury had occurred in the tissue at this time. The results o f the present study showed that Cd caused a change in subcellular distribut ion of tissue endogenous metals, which might reflect alteration of cellular functional activities. (C) 2000 Elsevier Science Ireland Ltd. All rights r eserved.