LEVELS OF SUPEROXIDE DISMUTASES, GLUTATHIONE, AND POLY(ADP-RIBOSE) POLYMERASE IN RADIORESISTANT HUMAN KB CARCINOMA CELL-LINE

In order to investigate the radioresistance mechanism of human carcino ma cells, we measured intracellular manganese-(Mn-) and copper/zinc-(C u/Zn-) superoxide dismutases (SODs), glutathione (GSH) and poly(ADP-ri bose) polymerase (PARP) in radioresistant N10 and its parental KB cell lines. The Mn-SOD level was 1.3-fold less in N10 than in KB, but Mn-S OD was induced at 1.3 to 1.5-fold higher level in N10 than in KB by X- irradiation (4 Gy). Cu/Zn-SOD in N10 showed a higher level than that i n KB both without and with irradiation. In addition, N10 had a 1.65-fo ld higher GSH level than did RE and became radiosensitive on treatment with buthionine sulfoximine, an inhibitor of GSH. Furthermore, PARP m RNA was highly expressed in N10 as compared to KB under unirradiated c onditions. X-Irradiation reduced the PARP mRNA level in KB in a time-d ependent manner, whereas the PARP mRNA level in N10 was still high at 6 h postirradiation. Assay for PARP activity demonstrated an approxima tely 3-fold higher activity in N10 than in KB under unirradiated condi tions. X-Irradiation caused a rapid induction of PARP activity within 1 h in both cell lines, but treatment of cells with nicotinamide, a PA RP inhibitor, markedly reduced the enzyme induction in N10, but not in KB, and potentiated the radiosensitivity in N10. These factors may al l contribute to the radioresistance of the N10 cell line.