Coordinate activation and regulation of quiescent metallothionein I and II genes in carcinogen-treated mouse thymic lymphoma cells.

Mouse thymus and some thymus-derived cell lines do not normally express metallothioneins (MTs), but these genes can be activated in at least one line (S49) by treatment with carcinogens. Almost half of cells converted to MT expression by carcinogens co-express both MT-I and MT-II, and levels of steady-state RNA from those activated genes are coordinately regulated by Cd. Nuclear transcription studies demonstrate that gene activation and regulation occurs at the level of transcription. Demethylation occurs 5' to each gene in lines expressing MTs. We detected no insertions, deletions, amplifications or rearrangements of the MT locus in lines expressing MTs.