Transformation of liver by SV-40 T-antigen in transgenic mice is unaffected by metallothionein

Transgenic mice expressing excess metallothionein-I and SV-40 T-antigen were generated to test the hypothesis that metal-lothionein may influence the rate of neoplastic transformation induced by T-antigen within the liver. The livers of the double transgenic mice grew at the same rate (to 32% body weight), had similar morphological and histological appearance, had similar chromosomal instability, and released identical amounts of serine and alanine aminotransferases into the blood as mice bearing SV-40 T-antigen alone, despite the fact that metallothionein levels were elevated five- to ten-fold. We conclude that elevated levels of metallothionein-I do not influence either the initial hyperplasia or the subsequent neoplastic transformation that is induced by T-antigen, which is thought to act by sequestering the P53 and retinoblastoma gene products.