REPAIR, REPOPULATION AND CELL-CYCLE REDISTRIBUTION IN RAT FOOT SKIN

The influence of the phenomena of the repair of sublethal damage, repo pulation and the role of the reassortment of surviving clonogenic targ et cells within the cell cycle have been examined in the foot skin of rats using a series of split dose experiments. The dose-related incide nce of moist desquamation was used as an end-point. Initially the iso- effect dose for moist desquamation (ED50) increased with an increasing time interval (1-22 h) between two equal fractions. This effect was a ttributed to the well established phenomenon of the repair of subletha l damage. This appeared to be maximal with a 22 h gap between fraction s. A further increase in the time interval, from 2-7 days, between two equal fractions resulted in a decrease in the ED50 value for moist de squamation. The phenomenon is most likely to be explained by a shorten ing of the cell cycle time in surviving epithelial target cells as rep opulation first initiated. With intervals between two fractions of gre ater than 10 days the ED50 for moist desquamation again increased. Thi s is likely to represent an increase in the number of epidermal target cells (repopulation). Further evidence for the effect of a reassortme nt of cells in the cell cycle has come from another study in which a h alf-tolerance priming dose of 16.8 Gy was followed by three daily frac tions starting 48 or 125 h after the priming dose. The ED50 for moist desquamation based on the total fractionated dose (three fractions) wa s significantly lower (P < 0.05) after the longer time interval, i.e. fractions given on days 5, 6 and 7 after the primary dose. These findi ngs were supported by the results of a cell proliferation kinetic stud y and jointly question the validity of a frequently made assumption of equal biological effect per fraction in a prolonged fractionated irra diation schedule. (C) 1998 Elsevier Science Ireland Ltd.