Enhancement of simian virus 40-induced transformation of nude mouse skin fibroblasts by 3-methylcholanthrene.

Abstract

Secondary cultures of newborn NMRI nu/nu (nude) mouse skin fibroblasts were used as targets for transformation by the combined administration of SV40 and 3-methylcholanthrene (MC). The SV40-induced transformation was enhanced both by pre- and post-treatment with MC at concentrations which themselves were nontransforming. The short pretreatment caused a 2-fold enhancement in the transformation frequency at a low concentration of MC that allowed greater than 50% of the cells to survive. A short post-treatment also caused a concentration dependent enhancement in SV40 transformation of the same magnitude. The long (72 h) post-treatment with MC increased virus transformation as much as 4.3-fold. In contrast, anthracene, a non-carcinogenic compound, had no effect on the viral transformation frequency. An analysis of the morphology of the foci revealed that long post-treatment with MC induced a high number of type I foci. Combination dishes lacked these foci almost completely, and the enhancement was due to the increased number of type II and type III foci.