Fraction size-dependent acute skin reaction of mice after multiple twice-a-day doses

To study the effect of multiple daily fractions on acute murine foot reaction, the left feet of C3Hf/Sed mice were irradiated by a Cs-137 irradiator at intervals of 6 and 18 hr, alternately. Fraction sizes ranged from 1 to 12 Gy, and various numbers of fractions were given. At the end of fractionation, a top-up dose of 20 Gy was administered. The overall treatment time ranged from 2 to 21 days. The average skin reaction from 10 to 35 days after completion of irradiations was determined. The skin reactions started from 8 to 27 days following the completion of irradiations. The skin reaction after fraction sizes of 3.5 and 5 Gy was dependent on the total dose. The skin reaction after fraction sizes of 1.5 and 2 Gy showed a biphasic response; at lower total doses, the skin reaction was proportional to the total dose, but at higher total dose, the skin reaction reached a plateau. The average skin reaction at the plateau with fraction sizes of 1, 1.5, and 2 Gy were 0.79 +/- 0.03, 1.12 +/- 0.13, and 1.37 +/- 0.06, respectively. The alpha/beta ratio for acute skin reaction following the twice a day scheme was 9.09 Gy (at dose/fraction greater than or equal to 3.5 Gy). The plateau may be attributed to the effect of accelerated proliferation and a balance between cell depletion and proliferation during twice-a-day irradiations. It is also suggested that twice-a-day irradiations induce more proliferation in skin than once a day treatments.