DEXAMETHASONE-INDUCED RADIORESISTANCE OCCURRING INDEPENDENT OF HUMAN PAPILLOMA-VIRUS GENE-EXPRESSION IN CERVICAL-CARCINOMA CELLS

Background: Inactivation of p53 by binding to simian virus 40-T antige n (SV40-T) and human papilloma virus type 16 protein E6 (HPV 16 E6) in transfected human diploid fibroblasts causes enhanced radioresistance . The aim of this study was to investigate the role of HPV 18 E6 and E 7 gene products with respect to radiosensitivity of two cervical carci noma cell lines. Materials and Methods: The two cervical carcinoma lin es C4-1 and SW 756 were used in which treatment with dexamethasone all ows to modulate expression levels of HPV 18 EG and E7 genes: upregulat ion in C4-1; downregulation in SW 756. Effects of treament with dexame thasone on plating efficiency and radiosensitivity were assessed using a clonogenic assay. Results: Treatment with dexamethasone increased p lating efficiency of the C4-1 cells, but did not affect plating effici ency of SW 756 cells. Treatment with dexamethasone induced enhanced ra dioresistance in both cell lines. Thus, in C4-1 cells the observed cha nges in radioresistance correlate to the enhancement in expression of HPV 18 genes E6/E7, whereas in SW 756, a reduced expression correlates negatively with the enhanced radioresistance. Conclusions: In C4-1 an d SW 756 cells, treatment with dexamethasone induces radioresistance, and changes in expression levels of HPV 18 genes E6 and E7 do not corr elate with the changes in radiosensitivity. Dexamethasone-induced radi oresistance has previously been observed in HeLa cells, another human cervical carcinoma cell line, This leads us to speculate that dexameth asone-induced radioresistance may be important in certain clinical sit uations, and that therefore, the phenomenon deserves further study.