Regulation of human metallothionein (MT) genes. Differential expression of MTI-F, MTI-G, and MTII-A genes in the hepatoblastoma cell line (HepG2).

We have analyzed the pattern of expression of three human metallothionein (MT) genes (MTI-F, MTI-G, and MTII-A) in the hepatoblastoma cell line, HepG2, in response to the metal ion inducers cadmium, copper, and zinc. The absolute number of transcripts of each of the three genes were measured, and the data clearly suggest differential regulation of these members of the MT gene family by the different inducers both in terms of the rate and the extent of transcript accumulation. The lowest levels of transcript accumulation was observed for MTI-F gene (maximum 4,000 molecules of mRNA per cell) and copper was shown to be its poorest inducer (up to 2,000 molecules per cell). Cadmium is the poorest inducer of MTI-G gene even though transcripts of this gene accumulated at comparatively higher levels than those of MTI-F. Copper- and zinc-induced MTI-G transcript accumulation was up to 12,000 molecules per cell whereas the corresponding value for cadmium was only 4,500. MTII-A was the only gene expressed in the absence of any externally added inducer. Also, in contrast to the MTI genes, the MTII-A gene was equally responsive to all the metal ions tested and the induced levels of accumulation were much higher (up to 75,000 molecules of MTII-A mRNA per cell).