Inhibition of adipose conversion of 3T3 fibroblasts by tumour promoters.

Abstract

TUMOUR-PROMOTING compounds are not themselves carcinogenic, but can induce skin tumours in mice pretreated with a subcarcinogenic dose of a chemical carcinogen1–3. They have been shown to produce many different biochemical and biological effects on cells3,4, but the mechanism of promotion is not known. Two recent reports describe the effects of the phorbol diester series of tumour promoters on cell differentiation in vitro. Cohen et al.5 observed that 12-O-tetradecanoyl-phorbol-13-acetate (TPA; phorbol myristate acetate), a potent promoter, inhibits myogenesis in chick embryo muscle cultures. We have reported6,7 that TPA and other tumour-promoting phorbol diesters inhibit spontaneous and induced differentiation of Friend erythroleukaemia cells in culture. We now describe another cell system, mouse preadipose cells, in which tumour promoters inhibit terminal differentiation, and confirm in these cells our original observation6 that there is a good correlation between the ability of a particular phorbol diester to promote tumours in mouse skin and its ability to inhibit terminal differentiation of cells in culture.