METALLOTHIONEIN DEFICIENCY PROMOTES MOUSE SKIN CARCINOGENESIS INDUCEDBY 7,12-DIMETHYLBENZ[A]ANTHRACENE

To investigate a possible involvement of metallothionein (MT) in chemi cal carcinogenesis, MT-I and MT-II gene-deficient [MT (-/-)] transgeni c mice and wild-type [MT (+/+)] control mice were topically applied at a single dose of 100, 250, 500, or 1000 mu g of 7,12-dimethylbenz[a]a nthracene (DMBA) on the dorsal skin and thereafter compared. After 14 weeks of DMBA treatment, the skin tumor occurred in MT (-/-) mice only and in a dose-dependent manner, whereas no change was observed in MT (+/+) mouse skin given the same DMBA treatment, The tumor cells showed proliferative activity, as shown by proliferative cell nuclear antige n staining, These results demonstrate that MT acts as an endogenous de fensive factor against DMBA-induced skin tumorigenesis.