LESS INITIAL REJOINING OF X-RAY-INDUCED DNA DOUBLE-STRAND BREAKS IN CELLS OF A SMALL-CELL (U-1285) COMPARED TO A LARGE-CELL (U-1810) LUNG-CARCINOMA CELL-LINE

Cells of a small cell lung carcinoma cell line, U-1285, and an undiffe rentiated large cell lung carcinoma cell line, U-1810, differ in radio sensitivity in parallel to the clinical radiosensitivity of the kind o f tumors from which they are derived. The surviving fraction at 2 Gy ( SF2) was 0.25 that of U-1285 cells and 0.88 that of U-1810 cells. We i nvestigated the induction of DNA double-strand breaks (DSBs) by X rays and DSB rejoining in these cell lines. To estimate the number of DSBs we used a model adapted for pulsed-field gel electrophoresis (PFGE). The induction levels were of the same magnitude (0.46 and 0.51 DSB/100 Mbp/Gy for U-1810 and U-1285 cells, respectively). These levels of in duction do not correlate with radiosensitivity as measured by cell sur vival assays. Rejoining of DSBs after doses in the range of 0-50 Gy wa s followed for 0, 15, 30, 60 and 120 min. We found a difference in the velocity of repair during the first hour after irradiation which is p arallel to the differences in radiosensitivity. Thus U-1810 cells exhi bit a fast component of repair, with about half of the DSBs being rejo ined during the first 15 min, whereas U-1285 cells lack such a fast co mponent, with only about 5% of the DSBs being rejoined after the same time. In addition there was a numerical albeit not statistical differe nce at 120 min, with more residual DSBs in the U-1285 cells compared t o the U-1810 cells.