Effects of very low dose-rate (90)Sr/(90)Y exposure on the acute moist desquamation response of pig skin.
OBJECTIVE
Previous data, predominantly involving high dose-rate fractionated irradiation with incomplete repair intervals, had indicated that the kinetics of repair of sublethal damage for acute radiation reactions in pig skin could best be defined by a biphasic repair model with half-times for repair of 0.2 and 5.4 h, partition coefficient 0.5. To further test the validity of this finding and obtain a better estimate of the repair rate of the slow component of repair, the acute response of pig skin to very low dose-rates (VLDR), originally estimated to be 0.0067-0.0244 Gy/min, was investigated as part of a 4 fraction irradiation protocol involving an overall treatment time of <9 days to avoid confounding factors such as induced repopulation and enhanced radio-sensitivity in this animal tissue.


METHODS
The flank skin of female Large White pigs, 3-4 months of age, was locally irradiated (8 sites/flank) with 22.5 mm diameter (90)Sr/(90)Y plaques. Irradiation with a 4 fraction protocol included 3 equal, high dose-rate, fractions with full repair, followed by a fourth VLDR fraction. The total doses administered were originally planned to represent the dose associated with the predicted ED(20), ED(50) and ED(80) (75% of total biological dose given at high dose-rate and 25% at VLDR) calculated on the basis of the repair kinetic parameters obtained from earlier studies. However, during the analysis a revision to the physical dosimetry was identified; this had been overlooked prior to the start of the study. Following completion of irradiation the irradiated sites were examined weekly and the presence or absence of moist desquamation recorded.


RESULTS
The incidence of moist desquamation was slightly higher than expected on the basis of the parameters used to calculate iso-effective doses, at least in part as a consequence of the change to the dosimetry. Using likelihood methods and the original dose estimates, the best model based estimate of the dose-rate correction factor for the LDR and VLDR plaques was 1.29. This was comparable with the physical calibration factor, median value 1.23. The VLDR fraction associated with a 50% incidence of moist desquamation, based on experimental observation, was 23.2+/-0.84, 27+/-2.6 and 30.1+/-3.2 Gy, for corrected VLDRs of 0.0247, 0.0093 and 0.0068 Gy/min, respectively. A biphasic model, which incorporated a dose-rate correction factor, provided a better fit than a monophasic repair model to the total data set, which now included the new VLDR data. Moreover, the monophasic repair model suggested a dose-rate correction factor of 1.63, well outside the range derived from the re-evaluation of the physical dosimetry.


CONCLUSIONS
Using the total data (with model based corrected dose-rates), the analysis revealed two components of repair with half-times of 0.103 (0.0594-0.177) and 2.97 (1.96-4.50) h; partition coefficient 0.375 (0.225-0.526). These are comparable with the estimates for other tissues (the CNS in particular) and suggest that the kinetics of repair may be relatively species and tissue independent with variation observed being more related to experimental design rather than any true differences.
Millar
W T
WT
Department of Radiation Oncology, University of Glasgow, Glasgow, UK.
Hopewell
J W
JW
D000818:Animals; D001610:Beta Particles; D004307:Dose-Response Relationship, Radiation; D005260:Female; D007700:Kinetics; D011836:Radiation Tolerance; D012867:Skin / Q000473:pathology / Q000528:radiation effects*; D013324:Strontium; D013552:Swine; D013997:Time Factors; D015021:Yttrium Radioisotopes
D015021:Yttrium Radioisotopes; D013324:Strontium