Recovery from sublethal damage during fractionated irradiation of human FaDu SCC.

摘要

BACKGROUND AND PURPOSE: 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. PATIENTS AND METHODS: FaDu tumours were transplanted s.c. into the right hind leg of NMRI nuu 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 3Gy in 18 or 36 days. All irradiations were given under clamp hypoxic conditions. Experimental endpoints were tumour control dose 50% (TCD(50)) and alpha/beta values without and after priming. RESULTS: Without priming TCD(50) increased with increasing number of fractions from 38.8Gy (95% CI 35;45) after single dose irradiation to 54.0Gy (42;57) after 8 fractions. No increase in TCD(50) 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 TCD(50) remained constant at 25Gy and after priming with 18 fractions in 36 days at 42Gy. The alpha/beta ratio without priming was 68Gy (42;127). After fractionated irradiation with 18 3-Gy fractions in 18 and 36 days the alpha/beta ratio increased to 317Gy (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.