THE COMBINED EFFECTS OF SUBLETHAL DAMAGE REPAIR, CELLULAR REPOPULATION AND REDISTRIBUTION IN THE MITOTIC-CYCLE .1. SURVIVAL PROBABILITIES AFTER EXPOSURE TO RADIATION

An analytical model is presented that describes radiation-induced cell ular inactivation in the presence of sublethal damage repair, cellular repopulation and redistribution in the mitotic cycle (the 3 Rs). The parameters of the model are measurable experimentally. Also taken into account are the initial age distribution of the cell population, the fact that subgroups of cells progress through the cycle at different s peeds, the effects of a dose of radiation on the duration of the four phases of the cycle (G(1), S, G(2), M), the possibility that a certain fraction of the cells are quiescent, and cell loss and/or cell remova l from the proliferating population. Survival probabilities are expres sed as linear-quadratic functions of dose where the coefficients alpha and beta as well as the recovery constant (t(0)) are taken to depend on the position of the cell in the mitotic cycle. Explicit analytical expressions for inactivation probability are given for clonogenic cell s exposed to continuous or fractionated radiation. Two model calculati ons are used to illustrate the formalism: in one. the redistribution o f cells during fractionated therapy is examined. In the other calculat ion, it is shown that it is sufficient to take into account difference s in proliferation rates and the change in the ratio alpha/beta within the generation cycle for cells that may have otherwise equal response to acute exposures to explain that in a fractionated treatment protoc ol late-responding cells are more sensitive to the dose per fraction t han early-responding cells. It is not necessary to invoke differences in radiosensitivity between these two classes of cells. (C) 1996 by Ra diation Research Society