Early and late response of the mouse limb to multifractionated x-irradiation

Abstract

Studies have been made of the response of C3H mouse hind limbs to various schedules of fractionated irradiation to elucidate the relative roles of repair and repopulation in determining early and late reactions. Early response has been measured in terms of desquamation and healing of skin covering the foot: late response has been evaluated in terms of deformity of the limb existing at 12 months after treatment. It was found that with 10 equal dose fractions, there was very little difference in response(approximately 6%) for early and late reactions, if treatments were given once, twice or four times per day. If the first nine treatments were given as small doses (200 rad compared with 400–700 rad per fraction) then the extent by which the dose must be decreased in reducing the fraction interval from 24 to 6 or 12 hr is 11% for the early reaction and 17% for the late response. In both cases the increased sensitivity changing from 24 hr to 6 hr fractionation intervals was greater (but not statistically significantly so) for the late than for the early reaction. Radiation given as 10, 20 or 30 “daily” fractions showed that, as overall treatment time increased: (a) the acute skin response (particularly the peak reaction) became less severe than predicted by the Ellis 12 formula, apparently because of rapid proliferation. (b) Late deformity reactions also became less severe at longer treatment times than predicted by the Ellis 12 formula although not to the same extent as did the mean early reaction. (c) The critical parameter determining tolerance as far as the early reaction is concerned is the dose per fraction rather than total dose for treatments given over longer times. A comparison of early versus late reactions showed that, at the longer treatment times, the late reaction was significantly more severe than was predicted from the early skin reaction.