REVERSION OF UV6-INDUCED TUMORIGENIC HUMAN HYBRID-CELLS TO THE NONTUMORIGENIC PHENOTYPE

Non-tumorigenic HeLa x skin fibroblast human hybrid cells were UVC-irr adiated (10 J/m(2)) and induced to neoplastic transformation with acco mpanying morphological change and expression of the HeLa tumour-associ ated antigen, intestinal alkaline phosphatase (IAP). A single-cell-der ived cell line was cloned out of a neoplastically transformed focus an d designated as UV-12. In low density culture, this cell line demonstr ated the ability to undergo reversion to a morphology similar to that of the nontumorigenic parent with accompanying, much reduced levels of IAP expression. The frequency of this reversion to low IAP expression increased with passage of low density cultures reaching 10(-2) at 26 passages. A revertant colony was selected and expanded into a cell lin e which was designated UV-12-RM-1. This cell line had a 67-fold reduct ion in IAP expression compared to UV-12 and demonstrated a much reduce d tumorigenic phenotype. A cell line reconstituted from a tumour deriv ed from this cell line demonstrated a high IAP expression level (3-fol d less than UV-12) and was highly tumorigenic. Six single-cell-derived lines were cloned from UV-12-RM-1 and all had low IAP expression. Of these, one demonstrated an aggressive tumorigenicity, four showed the reduced tumorigenic phenotype characteristic of UV-12-RM-1, and one (U V-12-RM-105) was non-tumorigenic. However, with passage in culture, th is latter cell line reverted to a weakly tumorigenic phenotype and a m uch elevated IAP level. It is hypothesised that the phenotypic shifts demonstrated by these UV-induced tumorigenic cells are under epigeneti c control, and that they are most likely a consequence of an underlyin g genetic instability in the survivors of UVC-irradiation.