Host: The Japan Radiation Research Society, Chairman of the 52nd Annual Meeting, Toshiteru Okubo (Radiation Effects Research Foundation)
The aim of this study was to clarify the effects of nitric oxide (NO) on radiation-induced cell killing and chromosomal aberrations in two human lung cancer cell lines with a different p53 gene status. Wild-type (wt) p53 and mutated (m) p53 cell lines were used which were derived from the human lung cancer H1299 cell line which is p53-null. The wtp53 and mp53 cell lines were generated by transfection of the appropriate p53 constructs into the parental cells. Cells were pre-treated with different concentrations of isosorbide dinitrate (ISDN, an NO donor) and/or 1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl) tetrahydroimidazole (c-PTIO, an NO scavenger), and then exposed to X-rays. Cellular sensitivity, apoptosis and chromosomal aberrations were scored using a colony-forming assay, Hoechst33342 staining and chromosomal banding techniques, respectively. In wtp53 cells, the induction of radioresistance and the inhibition of apoptosis and chromosomal aberrations were observed in the presence of ISDN at low 2-10 μM concentrations before X-irradiation. The addition of c-PTIO and ISDN into the culture medium 6 h before irradiation almost completely suppressed these effects. At high concentrations of ISDN (100-500 μM), however, clear evidence for radiosensitization, enhancement of apoptosis and chromosomal aberrations was detected. On the other hand, these phenomena were not observed in mp53 cells at either concentration range with ISDN. These results indicate low and high concentrations of NO radicals can choreograph inverse radiosensitivity, apoptosis and chromosomal aberrations in human lung cancer cells, and NO radicals can affect the fate of cells through the regulation of p53 gene expression.
