Dose-incidence relationships of reticulum cell sarcoma in mice. Observations and hypotheses at the cellular level

The final incidence of reticulum-cell sarcoma (RCS) in normal BCF1 mice is about 50% and is not changed by the administration of single acute whole-body doses of X-rays of up to 400 rads; higher doses produce a decrease of incidence down to a few per cent. Doses of 400 rads given to bone marrow before its injection into heavily irradiated syngenic hosts significantly increase the incidence and rate of appearance of RCS, in comparison with non-irradiated marrow: this observation suggests that marrow contains cells susceptible to radiation-induced neoplastic transformation. Recently, observations have been extended to include an endogeneous repopulating system where the marrow is irradiated in situ with moderate doses by a limb-shielding technique, and allowed to repopulate the rest of the body which is heavily irradiated. In these animals the incidence of RCS as a function of dose is described by a biphasic curve having a peak at about 500 rads. The initial ascending portion of this curve is in agreement with previous data obtained in the exogeneous system, and the final descending portion at doses in excess of 500 rads parallels the trend observed in whole-body irradiated animals. For a given dose level the moderately irradiated marrow, shielding of both legs results in a higher frequency of RCS than shielding of one leg only. These observations suggest the existence of a positive correlation between the mass of irradiated marrow (i.e. the number of susceptible cells) and the frequency of tumour appearance. It is possible, under a few reasonable simplifying assumptions and making use of independent estimates of the number of cells at risk and of their radiation response, to derive some relationship between the probability of cellular transformation and radiation dose: it is also possible to show that this relationship hold for various experiments and experimental conditions. (author)