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Inhibition of Induced Differentiation of C3H/10T Clone 8 Mouse Embryo Cells by Tumor Promoters¹

University of Southern California, Cancer Research Laboratories, Los Angeles, California 90033

C3H/10T cells were induced to differentiate into muscle cells by treatment with 5-azacytidine, and the effects of tumor promoters, nonpromoters, and inhibitors of tumor promotion on this induced differentiation were investigated. Cell morphology was dramatically changed within 30 min after treatment with phorbol ester-related tumor promoters and mezereine but not with other tumor promoters. There was a good correlation between the tumor-promoting activity of the compounds and their inhibitory action on differentiation except in case of phenobarbital; this promoter of liver carcinogenesis did not inhibit differentiation. Inhibitors of tumor promotion, dexamethasone, fluocinolone acetonide, retinoic acid, and antipain, also inhibited the 5-azacytidine-induced differentiation. When the cells were treated after induction of differentiation with 12-O-tetradecanoylphorbol-13-acetate, a potent tumor promoter, and simultaneously with one of those inhibitors of tumor promotion, the inhibitory action of 12-O-tetradecanoylphorbol-13-acetate was not affected. From these facts, it is evident that using a single phenomenon produced by one class of tumor promoter as a criterion for screening environmental tumor promoters is not justifiable.

¹ Supported by Contract NO1-CP-65831 from the National Cancer Institute and Grant R80-5208 from the Environmental Protection Agency.

² To whom requests for reprints should be addressed.

Received 8/ 9/79. Accepted 11/ 1/79.