The fractionated response of mouse stroma after X-rays and neutrons: influence of early vs late expression of damage.

Abstract

The sparing effect of dividing a radiation treatment into many small fractions is different for acutely responding tissues and those which have delayed expression of injury. We have used the Tumour Bed Effect assay (TBE) to investigate the influence of the time of damage expression on the response of the normally quiescent subcutaneous stroma. Implanted tumour cells provide an angiogenic stimulus which forces the vasculature to proliferate. The subcutaneous stroma of the mouse dorsum was irradiated with one to 32 equal fractions of X-rays, followed by a top-up dose of neutrons. CaNT cells were implanted into the treated site either within 3 days or not until 6 months after irradiation, to stimulate the expression of latent injury. The dose-response curves obtained for tumour growth in irradiated sites were much steeper at 1 to 3 days than at 6 months, suggesting some sort of repair of damage during this period. There was no suggestion that repair occurred preferentially after low doses per fraction and the alpha/beta ratio remained unchanged when the expression of stromal injury was delayed. The time of damage expression therefore seems unlikely to explain the difference in the alpha/beta ratios measured for early and late responding tissues. Rather, it seems to be determined by the proliferative status of the tissue at the time of irradiation.