Contrasting responses of normal and transformed rat tracheal epithelial cells to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate.

The data presented here are part of an ongoing effort to examine the response of rat tracheal epithelium to tumor promoting agents and to elucidate the mechanisms of tumor promotion in that epithelial tissue (see Steele, this volume). Previous studies indicated that airway epithelium is responsive to the tumor promoter TPA and that TPA can promote the tumor response in rat tracheal epithelium But what are the mechanisms involved? We have divided this question into two main elements: 1) Which stages of neoplastic development are affected by TPA, i.e., which preneoplastic cell populations are targets for TPA action resulting in the acceleration and enhancement of the process of neoplastic development? 2) What effects does TPA have on various preneoplastic cell populations and how do such effects result in promotion? The experiments discussed here relate to the second part of the question. They suggested that TPA elicits a marked cytotoxic response in stably transformed RTE cell variants (see Fig. 1). These preneoplastic cell variants are clearly different from untransformed RTE cells which are triggered into cell cycle as indicated by an increase in CFE. This difference between normal and transformed cells is of considerable interest in itself since it points to a fundamental, biochemical alteration in the transformed cells. Evidence exists that transformed RTE cell lines have TPA receptors and that at least some of the responses elicited by TPA exposure, such as the induction of ornithine decarboxylase activity, are receptor-mediated. Whether the cytotoxic response elicited by TPA is receptor-mediated is presently not known.(ABSTRACT TRUNCATED AT 250 WORDS)