PARENT SESSION

Experimental Therapeutics: Normal Tissue Response

(MS020) Effects of low dose-rate ⁹⁰Sr/⁹⁰Y exposure on the acute moist desquamtion response of pig skin.

Hopewell, John^*,1, Millar, William², ¹ Department of Clinical Oncology, Oxford, Oxon, UK² Department of Radiation Oncology, Glasgow, Strathclyde, UK

ABSTRACT- Introduction and objectives: Previous data for acute reactions in pig skin, following irradiation with multiple high dose-rate fractions (2 fractions/day) with intervals of between 0.17 - 8.0 h between fractions, were best described by a two component repair processes: half times of repair 0.17 and 5.4 h, partition coefficient 0.57. A single exponential repair model fitted the data less well: repair half-time 1.52 h. In order to further test the validity of these findings, specifically in relation to the slow half time for repair, the effects of irradiation with very low dose-rates, 0.0192 - 0.0053 Gy/min, have been examined. To avoid the introduction of additional confounding factors, such as induced-repopulation in surviving cells and the associated changes in radio-sensitivity, the overall exposure times were restricted ≤9 days, by adopting a 4 fraction protocol. The first three high dose-rate fractions were given 24 hours apart, with final fraction given at the very low dose-rates. Methods: Using the above parameters for the bi-phasic model the calculated total doses required to produce either a 20, 50 or 80% incidence of moist desquamations (ED₂₀, ED₅₀ and ED₈₀), given as three high dose-rate fractions followed by low dose-rate top-up doses, were administered. An interval of 24 - 36 h was allowed, after the completions of the fixed high dose-rate fractions, before the variable single low dose-rate fraction was given; 0.0192, 0.0072 or 0.0053 Gy/min; 17 - 18 fields were irradiated at each total dose level. Results: The observed ED50 values (±SE) for moist desquamation, based on the variable low dose-rate fraction, increased as the dose-rate decreased, i.e. 17.9 ± 0.65 Gy, 20.7 ± 2.0 Gy and 23.4 ± 2.5 Gy for dose-rates of 0.0192, 0.0072 and 0.0053 Gy/min, respectively. These ED₅₀ values are less than the values predicted of 20.24, 26.35 and 29.45 Gy, respectively, however, the revised repair kinetics were still consistent with the predictions, based on uncertainties on the original repair parameters. Conclusion: The results of experiments with multiple dose fractions, with incomplete repair, and those with extremely low dose-rates are consistent with the same bi-phasic repair kinetics. Use of the single repair parameter, derived from earlier studies, would have resulted in over-dosage in the present experiment.

Key words: Repair kinetics of sublethal damage, Low dose rate irradiation, acute skin reactions