Failure of phorbol ester TPA to promote growth of in vivo-initiated rat hepatocytes transferred into a culture system.

The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent promoter in epidermal carcinogenesis, on the growth of rat hepatocytes initiated in vivo and transferred into a culture system was investigated. The hepatocytes were isolated by enzymatic perfusion from the rat liver after 12 weeks of acetylaminofluorene feeding or 2--6 weeks of diethylnitrosamine treatment. TPA did not show any promotive effect in terms of the number and size of proliferative epithelial cell foci derived from initiated hepatocytes, in contrast to the remarkable effect of phenobarbital, which is a potent promoter in hepatocarcinogenesis. The results suggest the existence of organ or target cell specificity of promoters in the 2-stage concept of carcinogenesis.