Reversion of UVC-induced tumorigenic human hybrid cells to the non-tumorigenic phenotype.
Non-tumorigenic HeLa x skin fibroblast human hybrid cells were UVC-irradiated (10 J/m2) and induced to neoplastic transformation with accompanying morphological change and expression of the HeLa tumour-associated antigen, intestinal alkaline phosphatase (IAP). A single-cell-derived cell line was cloned out of a neoplastically transformed focus and designated as UV-12. In low density culture, this cell line demonstrated the ability to undergo reversion to a morphology similar to that of the non-tumorigenic 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 line which was designated UV-12-RM-1. This cell line had a 67-fold reduction in IAP expression compared to UV-12 and demonstrated a much reduced tumorigenic phenotype. A cell line reconstituted from a tumour derived from this cell line demonstrated a high IAP expression level (3-fold 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 (UV-12-RM-105) was non-tumorigenic. However, with passage in culture, this latter cell line reverted to a weakly tumorigenic phenotype and a much elevated IAP level. It is hypothesised that the phenotypic shifts demonstrated by these UV-induced tumorigenic cells are under epigenetic control, and that they are most likely a consequence of an underlying genetic instability in the survivors of UVC-irradiation.
Sun
C
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Department of Radiation Oncology, University of California-Irvine 92717, USA.
Antonionio
R J
RJ
Redpath
J L
JL
D000469:Alkaline Phosphatase / Q000378:metabolism; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology / Q000528:radiation effects*; D005347:Fibroblasts / Q000528:radiation effects; D006367:HeLa Cells / Q000528:radiation effects; D006801:Humans; D006822:Hybrid Cells / Q000473:pathology / Q000528:radiation effects; D007700:Kinetics; D008954:Models, Biological; D010641:Phenotype; D014466:Ultraviolet Rays
D000469:Alkaline Phosphatase