Tumor‐promoting activity of epstein‐barr‐ virus‐inducing factor transforming growth factor type beta (EIF/TGF‐β) is due to the induction of irreversible transformation

EBV‐inducing factor/transforming growth factor type beta (EIF/TGF‐β) exhibits tumor‐promoting activity for C3H‐10T1/2 mouse fibroblasts in vitro. Treatment of C3H 10 T 1/2 fibroblasts seeded at low density with initiating doses of UV light, followed by culture in the presence of EIF/TGF‐β leads to the appearance of foci of stably transformed cells that have the potential to grow in soft agar. The promoting effect depends both on the dose of EIF/TGF‐β applied and its continuous presence for 2 to 3 weeks. In addition to its pro‐carcinogenic effect in tumor promotion, EIF/TGF‐β exhibits a strong negative effect on transformed cells surrounded by normal cells, indicating a dual role of EIF/TGF‐β in carcinogenesis. The lack of completely transformed individual cells in the initiated cell population and the negative effect of EIF/TGF‐β on transformed cells in contact with normal cells exclude any possible explanation of the tumor‐promoting effect of EIF/TGF‐β as being the result of a selection process due to the establishment of growth advantages for cells transformed by the initiator. The data, in fact, indicate that tumor promotion by EIF/TGF‐β implies the stable acquisition of distinct qualitative changes by the cells.