p53-dependent radioresistance in ovarian carcinoma cell lines

In the present study, we investigated the radiosensitivity profiles of three established human ovarian carcinoma cell lines, PA-1, Caov-3, and SK-OV-3, using the adenosine triphosphate-cell viability assay (ATP-CVA). We have correlated radioresponsiveness with the p53 status and the p53 accumulation after irradiation as well as with the Bcl-2 expression and the growth rate of these cell lines. The p53 status was examined by immunocytochemistry and a functional assay (functional analysis of separated alleles in yeast, FASAY); the p53 accumulation was determined by immunocyotochemistry and flow cytometry. Futhermore, the Bcl-2 expression before and after irradiation was examined by immunocytochemistry. PA-1, expressing wildtype p53, showed an unequivocal; accumulation of p53 protein following exposure to irradiation. This cell line was found to be strongly sensitive to irradiation. The two p53 mutant cell lines Caov-3 and SK-OV-3 showed radioresistance at different degrees and irradiation did not result in p53 accumulation. None of the cell lines examined expressed Bcl-2 protein and no change was seen after irradiation. Furthermore, the most sensitive cell line to irradiation, PA-I, showed the highest proliferative activity, while Caov-3 and SK-OV-3, the more resistant cell lines, exhibited lower growth rates. Our findings indicate that the presence of p53 protein is a possible determinant for the cytotoxicity induced by irradiation in the investigated ovarian carcinoma cell lines. Bcl-2 expression does not seem to determine the response to irradiation in these cell lines. Additionally, an association between radioresponsiveness and the growth rate is suggested in PA-1, Caov-3, and SK-OV-3. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.