Recovery from sublethal damage during fractionated irradiation of human FaDu SCC.
OBJECTIVE
The present study addresses whether recovery of sublethal damage in tumours may change during fractionated irradiation in FaDu human squamous cell carcinoma and whether such an effect might contribute to the pronounced time factor of fractionated irradiation previously found in this tumour.


METHODS
FaDu tumours were transplanted s.c. into the right hind leg of NMRI nu/nu mice. Single doses or 2, 4, and 8 equal fractions in 3.5 days were applied in previously unirradiated tumours and after priming with 18 fractions of 3 Gy in 18 or 36 days. All irradiations were given under clamp hypoxic conditions. Experimental endpoints were tumour control dose 50% (TCD50) and alpha/ beta values without and after priming.


RESULTS
Without priming TCD50 increased with increasing number of fractions from 38.8 Gy (95% CI 35;45) after single dose irradiation to 54.0 Gy (42;57) after 8 fractions. No increase in TCD50 when given in 1, 2, 4, or 8 fractions in 3.5 days was found after priming with 18 3-Gy fractions in 18 and 36 days. After priming with 18 fractions in 18 days TCD50 remained constant at 25 Gy and after priming with 18 fractions in 36 days at 42 Gy. The alpha/beta ratio without priming was 68 Gy (42;127). After fractionated irradiation with 18 3-Gy fractions in 18 and 36 days the alpha/beta ratio increased to 317 Gy (38; infinity) and to infinite, respectively.


CONCLUSIONS
Our results indicate that clonogenic cells in FaDu tumours lose entirely their capacity to recover from sublethal radiation damage during fractionated irradiation. Therefore, an increased repair capacity as an explanation for the pronounced time factor of fractionated irradiation in this tumour can be ruled out.
Petersen
Cordula
C
Clinic of Radiation Oncology, Medical Faculty Carl Gustav Carus, University of Technology, Fetscherstr. 74, 01307 Dresden, Germany.
Zips
Daniel
D
Krause
Mechthild
M
Völkel
Wolfram
W
Thames
Howard D
HD
Baumann
Michael
M
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D002470:Cell Survival; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D011836:Radiation Tolerance; D014183:Transplantation, Heterologous