EXPOSURE OF HUMAN PROXIMAL TUBULE CELLS TO CYTOTOXIC LEVELS OF CDCL2 INDUCES THE ADDITIONAL EXPRESSION OF METALLOTHIONEIN 1A MESSENGER-RNA

Humans, in contrast to animals, have a complex expression of metalloth ionein (MT) genes which involves many MT isoforms encoded by a family of genes containing an upper limit of 12 possible functional genes. It is unknown if these human isoforms of MT have distinct functions or i f they simply represent a non-essential duplication of gene function. In the present study, MT protein and mRNA for the MT-2A, MT-1A, B, E, F, and G genes was determined for 3 isolates of human proximal tubule (HPT) cells having distinct sensitivities to cadmium. For all 3 HPT is olates, the expression of MT protein and mRNA for the MT-2A, MT-IF, MT -IF and MT-IG isoforms was similar among the isolates and demonstrated no correlation to lethality. However, each isoform mRNA was expressed at different levels when compared to one another. In contrast, the ex pression of MT-IA mRNA differed in expression and correlated with the differing lethalities displayed by each isolate. The finding of differ ent profiles of mRNA expression provides evidence that the MT isoforms may have unique functions and that mRNA for the MT-1A gene could be a potential marker for heavy metal exposure and/or toxicity.