The radioenhancement of two human head and neck squamous cell carcinomas by 2'-2' difluorodeoxycytidine (gemcitabine; dFdC) is mediated by an increase in radiation-induced residual chromosome aberrations but not residual DNA DSBs

• Published in: Mutation research Vol. 527; no. 1-2; pp. 15 - 26
• Main Authors: ROSIER, Jean-Francois, MICHAUX, Lucienne, AMEYE, Geneviève, CEDERVALL, Björn, LIBOUTON, Jeanne-Marie, OCTAVE-PRIGNOT, Michèle, VERELLEN-DUMOULIN, Christine, SCALLIET, Pierre, GREGOIRE, Vincent
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 19.06.2003
• Subjects: Antineoplastic Agents - pharmacology; Biological and medical sciences; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - pathology; Chromosome Aberrations - drug effects; Chromosome Aberrations - radiation effects; Combined Modality Therapy; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacology; DNA Damage - drug effects; DNA Damage - radiation effects; DNA, Neoplasm - drug effects; DNA, Neoplasm - radiation effects; Fundamental and applied biological sciences. Psychology; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - radiotherapy; Humans; Molecular and cellular biology; Molecular genetics; Mutagenesis. Repair; Radiation Tolerance; Radiation, Ionizing; Radiation-Sensitizing Agents - pharmacology; Time Factors; Tumor Cells, Cultured; Chromosomal aberration; Human; Squamous cell carcinoma; Gemcitabine; DNA DSB; Double strand break; PFGE; Cell line; DNA; Irradiation; Head and neck; FISH; Repair; Chromosome aberrations
• ISSN: 1386-1964; 0027-5107; 1879-2871
• DOI: 10.1016/S0027-5107(03)00053-8

The present study aimed at investigating if 2'-2' difluorodeoxycytidine (dFdC) radioenhancement was mediated by an effect on induction and/or repair of radiation-induced DNA DSBs and chromosome aberrations in cells with different intrinsic radiosensitivity. Confluent human head and neck squamous cell carcinoma cell lines designated SCC61 and SQD9 were treated with 5 microM dFdC for 3 or 24 h prior to irradiation. DNA DSBs induction and repair were analyzed by PFGE. Radiation-induced chromosome aberrations were examined with a FISH technique. In both cell lines, dFdC did not modify radiation-induced DNA DSBs in a dose range between 0 and 40 Gy. After a single dose of 40 Gy, dFdC affected neither the kinetic of repair nor the residual amount of DNA DSBs up to 4 h after irradiation. Whereas dFdC did not increase the induction of chromosome aberrations, after a single dose of 5 Gy, the percentage of aberrant cells and the number of aberrations per aberrant cells were significantly higher in combination with dFdC. Our data suggest that under experimental conditions yielding substantial radioenhancement, dFdC decreases the repair of genomic lesions inducing secondary chromosome breaks but has no effect on DNA DSBs repair as measured by PFGE.