The effect of irradiation on function in self-renewing normal tissues with differing proliferative organisation

Abstract

The primary effect of irradiation on self-renewing normal tissues is sterilisation of their proliferative cells, but how this translates into failure of tissue function depends on the mode of organisation of the tissue concerned. It has recently been suggested (Michalowski, 1981) that proliferative normal tissues may be classed as "hierarchical" (like haemopoietic tissues) or as "flexible" (like liver parenchyma) and that radiation injury to tissue function develops by different pathways in these tissues. Mathematical model studies confirm the different radiation responses of differently organized tissues. Tissues of the "flexible" or "F-type" category display a variety of novel radiobiological properties, different from those of the more familiar "hierarchical" or "H-type" tissues. The "F-type" responses are strongly influenced by radiation-sterilised ("doomed") cells, and it is suggested that the rôle of "doomed" cells has been undervalued relative to that of clonogenic survivors. Since "F-type" tissues have characteristically low rates of cell renewal, it is possible that these tissues are preferentially responsible for late effects of irradiation in clinical radiotherapy.

Normal tissue complications after radiation therapy

“…After high doses, complete denudation of such tissues occurs at a time equivalent to the lifetime of new mature cells, including cells produced by any radioresistant precursor cells. This pattern of response has been well described for many types of renewal tissues (3,4).…”

“…These populations of parenchymal cells, such as those in the liver and kidney, are capable of function as well as induced multiplication. They have been called flexible populations (3), in contrast to the hierarchical populations in renewing tissues.…”

“…Detailed studies on telangiectasia provide a very clear example of this effect (7). Also, there is an increasing incidence of injury with increasing doses before the plateau in timing occurs at a very high dose (3).…”

Repopulation in Human Tumors: A Biological Back-Ground for Fractionation in Radiotherapy

“…The role of repopulation in normal tissue reactions following a cytotoxic insult markedly varies with the turnover rate of the cell population (13, 40, 59). In slowly proliferating tissues which are responsible for the late effects, the proliferative rate, as assessed by the labelling index, is not significantly increased during the first few weeks following an irradiation or the administration of cytotoxic drugs.…”

Influence of Pancreatic Secretion on Late Radiation Enteropathy in the Rat

“…Whereas many authors regard differences in proliferation rate or proliferative organisation as the main reason for the difference between early and late reacting tissues (7, 20,22), others maintain that the late changes following irradiation are secondary to vascular damage (8, 10). Increased endothelial permeability following irradiation is considered the primary lesion leading to leakage of fluids and proteins, and subsequent late fibrosis of the vessel wall and perivascular tissue (10).…”