Radiosensitivity of peripheral blood lymphocytes from healthy donors and cervical cancer patients; the correspondence of in vitro data with the clinical outcome.
The reliability of a particular in vitro parameter as potential prognostic biomarker of individual radiosensitivity is still discussed. Therefore, several in vitro radiation-induced cellular endpoints including initial, oxidative and residual DNA damage and the rate of DNA repair were assessed in peripheral blood lymphocytes (PBL) from healthy donors and patients with carcinoma of the cervix using the alkaline single cell gel electrophoresis (the comet assay). PBL from cancer patients were analyzed three times during the course of therapy, prior, in the middle (25-27 Gy) and after the radiotherapy. Interindividual differences in radiation-induced DNA damage and in the kinetics of strand break rejoining were determined within both groups. Significantly higher level of mean background and oxidative DNA damage was estimated in the cancer patient cohort than in the healthy subject group; however similar mean values of the initial DNA damage and the rate of DNA repair kinetics were found in both groups. No adaptive response was determined in PBL from cancer patients due to radiotherapy. The acute radiation toxicity and the clinical outcome were scored according to the criteria as proposed by the National Cancer Institute. A substantial delay in DNA strand break rejoining was determined in cancer patients suffering from adverse side effects (G2+) in comparison to persons with no or very mild radiation toxicity (G0-G1) (p<0.05). The recurrence of disease has been associated with a lower initial DNA damage and slope value of dose-response effect, and increased rate of DNA repair. Results from this pilot study suggest that the residual DNA damage level might be a promising prognostic biomarker of acute radiation morbidity; however, further study is necessary to validate this finding.
Gabelova
A
A
Laboratory of Mutagenesis and Carcinogenesis, Cancer Research Institute, Slovak Academy of Sciences, Vlárska 7, Bratislava, Slovakia. alena.gabelova@savba.sk
Farkasova
T
T
Gurska
S
S
Machackova
Z
Z
Lukacko
P
P
Witkovsky
V
V
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000532:radiotherapy*; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008214:Lymphocytes; D008875:Middle Aged; D010865:Pilot Projects; D011379:Prognosis; D011446:Prospective Studies; D011836:Radiation Tolerance; D011878:Radiotherapy / Q000009:adverse effects; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000532:radiotherapy*