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 undifferentiated large cell lung carcinoma cell line, U-1810, differ in radiosensitivity in parallel to the clinical radiosensitivity of the kind of 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 investigated 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 induction do not correlate with radiosensitivity as measured by cell survival assays. Rejoining of DSBs after doses in the range of 0-50 Gy was 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 parallel to the differences in radiosensitivity. Thus U-1810 cells exhibit a fast component of repair, with about half of the DSBs being rejoined during the first 15 min, whereas U-1285 cells lack such a fast component, with only about 5% of the DSBs being rejoined after the same time. In addition there was a numerical albeit not statistical difference at 120 min, with more residual DSBs in the U-1285 cells compared to the U-1810 cells.
Department of Medical Radiation Physics, Karolinska Institutet, Stockholm, Sweden.
B
B
Cedervall
F
F
Sirzea
O
O
Brodin
R
R
Lewensohn
D018287:Carcinoma, Large Cell; D018288:Carcinoma, Small Cell; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects*; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000302:isolation & purification / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014965:X-Rays
D004273:DNA, Neoplasm