Analysis by alkaline comet assay of cancer patients with severe reactions to radiotherapy: defective rejoining of radioinduced DNA strand breaks in lymphocytes of breast cancer patients.
Therapeutic exposure to ionising radiation reveals inter-individual variations in normal tissue responses. To examine whether a defect in DNA repair capacity might be involved in such hypersensitive phenotypes, we analysed, using the alkaline comet assay, the response as a function of time to in vitro irradiation at 5 Gy of lymphocytes from 17 breast cancer and 9 Hodgkin's disease patients who developed severe reactions to radiotherapy in comparison with 22 patients with "average" reactions and 24 healthy donors. A difference between breast cancer over-reactors and both patients with normal reactions and healthy donors was observed 30 and 60 min after exposure. A subgroup of breast cancer over-reactors (7/17) reproducibly demonstrated increased levels of residual damage. When the kinetic analyses were prolonged to 120 min, results were in favour of delayed kinetics of rejoining in these patients. Among Hodgkin's disease over-reactors, only one patient showed defective repair. Interestingly, all patients with the most severe complications (grade 4 RTOG/EORTC), i.e., 5 breast cancer and 1 Hodgkin's disease, showed impaired rejoining. Our results suggest that impairment in DNA strand break processing may be associated, in specific subgroups of breast cancer patients, with an individual risk of major toxicity of radiation therapy. Thus, the alkaline comet assay appears to be useful for documenting the DNA repair phenotype in cancer patients.
Alapetite
C
C
UMR 218 CNRS/IC, Institut Curie-Recherche, Paris, France. Claire.Alapetite@curie.net
Thirion
P
P
de la Rochefordière
A
A
Cosset
J M
JM
Moustacchi
E
E
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D004247:DNA / Q000032:analysis / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D004587:Electrophoresis, Agar Gel / Q000379:methods*; D005260:Female; D006689:Hodgkin Disease / Q000097:blood / Q000532:radiotherapy; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D011878:Radiotherapy / Q000009:adverse effects*; D013997:Time Factors
D004247:DNA