title: Differences in the level of DNA double-strand breaks in human tumour cell lines following low dose-rate irradiation.
abstract: It is now well accepted that differences exist in the intrinsic radiosensitivity of human tumour cells although the molecular basis of this is still unclear. Current evidence suggests that of the lesions induced in DNA by ionising radiation, double-strand breaks (DSB) are the most closely linked to cell death. In this study, levels of DSB were measured by neutral filter elution under conditions of both repair inhibition and maximum recovery and compared with clonogenic survival curves for high (HDR) and low dose-rate (LDR) irradiation in human carcinoma lines of differing radiosensitivity. Four human lung carcinoma lines were used, two small-cell (SCLC; HC12 and HX149) and two non-small cell lines (NSCLC; HX147A7 and HX148G7). Cell survival was measured by soft agar and monolayer colony-forming assays as appropriate and a large variation in sensitivity of the cell lines was seen (alpha values of 0.06 to 0.56 Gy-1). We have previously reported that the damage induced at high dose rate does vary in these cell lines but not in a way which correlates with their cell survival response [5]. Following irradiation to 15 Gy at low dose rate essentially no DSBs were detected in any of the four lines but at 70 Gy the more sensitive SCLC showed more residual damage than in the more radioresistant NSCLC lines. The prime determinant of the difference between the LDR and HDR damage curves is likely to be repair occurring during irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Radiotherapy Research Unit, Institute of Cancer Research, Sutton, Surrey, U.K.
authors.forename: A M
authors.initials: AM
authors.lastname: Cassoni
authors.forename: T J
authors.initials: TJ
authors.lastname: McMillan
authors.forename: J H
authors.initials: JH
authors.lastname: Peacock
authors.forename: G G
authors.initials: GG
authors.lastname: Steel
mesh_terms: D002470:Cell Survival / Q000528:radiation effects; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*; D011879:Radiotherapy Dosage; D014407:Tumor Cells, Cultured / Q000528:radiation effects
chemical_list: D004273:DNA, Neoplasm