RESUMO
Five mutant Chinese hamster cell lines deficient in DNA repair with the corresponding parental cell lines were used to determine their sensitivity to cisplatin, 5-fluorouracil and gemcitabine. The mutations in the cell lines led to defective single strand break repair (EM-C11), defective recombination mediated repair (irs1SF), defective double strand break repair (XR-V15B, a Ku-80 mutant and CR-C1, a DNA-PKcs mutant) and an AT-like mutation (VC-4). All mutant cell lines had an impaired doubling time during exponential growth and an increased sensitivity to X-irradiation. We may conclude that for cisplatin-induced cytotoxicity the homologous recombination-associated DNA repair plays an important role in the repair of the cisplatin induced lesions, confirming previous results. In 5-FU and gemcitabine induced toxicity to cells, repair processes involved with radiation-induced damage were not implicated. This is in striking contrast to the role of cisplatin in radiosensitization where inhibition of the NHEJ pathway is implicated, and to the role of gemcitabine in sensitization where specific interference with the HR pathway is implicated.
Assuntos
Cisplatino/toxicidade , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/efeitos da radiação , Desoxicitidina/análogos & derivados , Desoxicitidina/toxicidade , Fluoruracila/toxicidade , Animais , Antimetabólitos Antineoplásicos/toxicidade , Células CHO , Divisão Celular/efeitos dos fármacos , Divisão Celular/efeitos da radiação , Linhagem Celular , Cricetinae , DNA/genética , Relação Dose-Resposta a Droga , Raios X , GencitabinaRESUMO
PURPOSE: To determine whether measurement of chromosome aberrations by fluorescence in situ hybridization (FISH) predicts cell survival after irradiation at different dose-rates and after radiosensitization by bromodeoxyurdine (BrdU) in a lung carcinoma cell line. MATERIALS AND METHODS: The human lung carcinoma cell line SW1573 was irradiated at high dose-rate (HDR: 0.8 Gy min-1) or at pulsed low dose-rate (p-LDR: average dose-rate 1 Gy h-1) with or without radiosensitization by bromodeoxyuridine (BrdU). Cell survival was determined by clonogenic assay. Chromosome aberrations (colour junctions) were measured by whole-chromosome FISH of chromosome 2 and 18 and were scored according to the PAINT method. RESULTS: Clear radiosensitization by BrdU was observed both after HDR and p-LDR irradiation. Chromosome 18 was more radiosensitive than chromosome 2. There was a good correlation between induction of colour junctions and cell survival both after HDR and p-LDR irradiation and after radiosensitization by BrdU. CONCLUSIONS: Determination of chromosome aberrations by FISH can predict cell survival after different dose-rates and after radiosensitization by BrdU