Radiation-induced DNA damage and repair in lymphocytes from breast cancer patients and their correlation with acute skin reactions to radiotherapy.
OBJECTIVE
Repair of radiation-induced DNA damage plays a critical role for both the susceptibility of patients to side effects after radiotherapy and their subsequent cancer risk. The study objective was to evaluate whether DNA repair data determined in vitro are correlated with the occurrence of acute side effects during radiotherapy.


METHODS
Breast cancer patients receiving radiation therapy after a breast-conserving surgery were recruited in a prospective epidemiologic study. As an indicator for clinical radiosensitivity, adverse reactions of the skin were recorded. Cryo-preserved lymphocytes from 113 study participants were gamma-irradiated with 5 Gy in vitro and analyzed using the alkaline comet assay. Reproducibility of the assay was determined by repeated analysis (n = 26) of cells from a healthy donor. A coefficient of variation of 0.3 was calculated.


RESULTS
The various parameters determined to characterize the individual DNA repair capacity showed large differences between patients. Eleven patients were identified with considerably enhanced DNA damage induction, and 7 patients exhibited severely reduced DNA repair capacity after 15 and 30 min. Six patients were considered as clinically radiosensitive, indicated by moist desquamation of the skin after a total radiation dose of about 50 Gy.


CONCLUSIONS
Using the alkaline comet assay as described here, breast cancer patients were identified showing abnormal cellular radiation effects, but this repair deficiency corresponded only at a very limited extent to the acute radiation sensitivity of the skin. Because impaired DNA repair could be involved in the development of late irradiation effects, individuals exhibiting severely reduced DNA repair capacity should be followed for the development of late clinical symptoms.
Popanda
Odilia
O
Division of Toxicology and Cancer Risk Factors, German Cancer Research Center, Heidelberg, Germany. o.popanda@dkfz.de
Ebbeler
Reinhard
R
Twardella
Dorothee
D
Helmbold
Irmgard
I
Gotzes
Florian
F
Schmezer
Peter
P
Thielmann
Heinz Walter
HW
von Fournier
Dietrich
D
Haase
Wulf
W
Sautter-Bihl
Marie Luise
ML
Wenz
Frederik
F
Bartsch
Helmut
H
Chang-Claude
Jenny
J
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000532:radiotherapy / Q000601:surgery; D015331:Cohort Studies; D020552:Comet Assay; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry / Q000528:radiation effects*; D015412:Mastectomy, Segmental; D008875:Middle Aged; D011446:Prospective Studies; D011836:Radiation Tolerance; D011855:Radiodermatitis / Q000209:etiology* / Q000235:genetics; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects*; D011882:Radiotherapy, High-Energy / Q000009:adverse effects*
D004247:DNA