CELL-SURVIVAL DATA AND THE IRRADIATION RESPONSE OF SOME NORMAL TISSUES.

Abstract

The determination of cell-survival curves in vitro (Puck and Marcus, 1956) and in vivo (Hewitt and Wilson, 1959) and the impressive uniformity of their chief parameters (Morkovin and Feldman, 1960) for a wide range of cell types has led to many speculations regarding the application of cell-survival curves to the explanation of the response of tumours and other tissues to irradiation. An important virtue of cell-survival data is that they refer to and measure those cells which have not lost their reproductive integrity. They thus specify radiosensitivity much more definitely than is often the case in other looser clinical and biological uses of the term. Thus, tissues which show a great deal of cellular damage are often described as very radiosensitive whereas this observation may be simply due to such a rapid turnover of the cells that the irradiation damage to them is made manifest. Another tissue with a slow rate of cell turnover could be equally damaged by the same dose of radiation, but the injury would not be shown to the same degree. Such tissues are then often described, erroneously, as radioresistant. If these facts are borne constantly in mind, many normal tissue responses to irradiation which at first appear to be most unusual become somewhat easier to understand. Indeed, if cell-survival curves really have the significance many now attribute to them, it is important that it be possible to explain the tissue-cellular responses to irradiation in the simple terms of these curves without resource (as is often the case) to a wide variety of hypotheses for which there is little or no experimental evidence. Accordingly, an attempt has been made to pursue such a line of reasoning with reference to some admirably detailed results that have been made available recently (Quastler et al., 1959; Lamerton, 1963) concerning the effect of low-dose rate, continuous gamma radiation upon cell proliferation in the rat intestine, and also with reference to other results concerning the effect of single acute doses of radiation upon the same tissue (Quastler, 1956; Quastler and Zucker, 1959; Corp and Neal, 1959; Bloom, 1950). Cell Kinetics of the Rat Intestine (Quastler et al.; Lamerton): Normally cells produced by cell division in the crypts enter the villus, pass through it to mature, and ultimately succumb. The average number of proliferating cells in the crypt is about 850 per crypt. The mean generation time of the cells has been determined as approximately twelve hours; 850 cells, then, are produced per crypt approximately every twelve hours to pass on into the villus, i.e., about 71 cells per hour pass on. In a steady state this is also the rate of loss of cells from the villus. A cell takes about eighteen and a half hours to migrate the whole length of the villus, so that the total average number of cells in the villus will be 71 × 18.5, or about 1,320 cells.