Metallothionein accretion in human hepatic cells is linked to cellular proliferation

The basal amounts of metallothionein (MT) and its rates of biosynthesis were compared in resting and proliferating Chang liver (CCl-13) cells. In resting cells the total amounts of the detectable isoforms MT-2 and MT-1e were approx. 1.6x10(6) and 4x10(5) molecules per cell respectively. In exponentially growing cultures the cellular contents of both isoforms increased co-ordinately approx. 4-fold and decreased again to the initial values within 48 h after entering density-mediated growth arrest. As documented for MT-2 its transient accretion was attributable to a 10-fold rise in the rate of biosynthesis of this protein during the growth phase. Measurements of the relative amounts of MT-2 mRNA indicated the occurrence of a more than 50% increase within the first 12 h after subculturing of the cells, followed by a return to basal levels thereafter. These results denote a direct link between the programming of MT synthesis and proliferation and thus attest to a central housekeeping function of the MTs.