Radiobiology of the C3H Mouse Mammary Carcinoma: The Effect of Body Dose on the Radiocurability of the Tumour Treated In Situ

Abstract

IN a previous experiment (Cohen and Cohen, 1953) the LD50 for the treatment of the C3H adenocarcinoma in situ was found to be 5700 (+ 140) r. It was considered that this quantity was not necessarily a fixed property of the tumour, but was probably dependent upon the state of the host. Both spontaneous and radiation-induced regression of tumours are known to be associated with stromal and lymphoid reactions or similar manifestations of a resistance mechanism in the host (Murphy, 1926). It has been shown that total body radiation can affect the host to such an extent that spontaneous regression of a homoplast can be reversed (Cohen and Cohen, 1951) and even genetic resistance to a heterologous implant can be overcome (Clemmesen, 1938). It seemed likely, therefore, that total body irradiation would also tend to prevent radiation-induced regression of tumours, and might consequently modify the curative dose for treatment in situ. Accordingly, in the following experiment, the quantitative effect of total body radiation of the host on the radiocurability of the C3H mammary tumour is demonstrated. MATERIALS AND METHODS.Animals.The mice used in this investigation are a registered subline, designated C3H/Cg, originating from a high mammary tumour strain C3H/Jax, which has been maintained in this laboratory since 1951. The technique of homoiotransplantation and irradiation of tumour homoplasts in situ is identical with that reported in a previous paper (Cohen and Cohen, 1953). Radiation factors.The total body dose was given with 240 kV., 1 mm. Cu + 1 mm. Al filter, HVL 1-5 mm. Cu, FSD 50 cm.; the mice being treated en masse in a shallow cardboard box measuring 20 x 20 x 3 cm., at a surface dose rate of 50 r/min. At this quality of radiation, the dosage distribution throughout the body of each mouse is practically homogeneous.Experimental design.In a recent paper (Kaplan and Brown, 1952) it was shown that a maximal depression of host resistance to tumour induction with a minimal mortality of mice could be obtained by total body radiation delivered in 4 fractions at four-

Radiobiology of the C3H Mouse Mammary Carcinoma: Effect of Immunogenetic Factors on the Radiosensitivity of the Tumour Treated In Situ

“…It is concluded, therefore, that the reaction of the hybrid host to the parent strain tumour is the primary determining factor. A similar phenomenon, in which host-reaction seemed to determine the radiosensitivity of the tumour, was observed when induced radiosensitivity in previously attenuated homoplasts growing in C3H mice was lost when these were transplanted to other hosts (Cohen and Cohen, 1954).…”

“…The magnitude of this ratio compared to its standard error shows the difference in radiosensitivity of the two groups to be highly significant (p < 0-0001). (Cohen and Cohen, 1954).…”

“…Having established the median effective dose for the treatment of the C3H mammary adenocarcinoma in situ, it was subsequently demonstrated thatwhen the resistance of the tumourbearing animals was deranged by total-body irradiation, a significant decrease in the radiosensitivity of the tumour occurred (Cohen andCohen, 1953a, 1953b). Conversely, a state of relative genetic resistance in the host can result in a marked increase in the radiosensitivity of a tumour.…”

“…Having established the median effective dose for the treatment of the C3H mammary adenocarcinoma in situ, it was subsequently demonstrated thatwhen the resistance of the tumourbearing animals was deranged by total-body irradiation, a significant decrease in the radiosensitivity of the tumour occurred (Cohen and Cohen, 1953a, 1953b (1940) showed that F2 hybrids, a cross between low-tumour and high-tumoiir mouse strains, bearing a mammary carcinoma originating in the high-tumour parent stock, exhibited a natural resistance evidenced by a moderate incidence of of spontaneous regressions, and were readily cured with a relatively small dose of radiation known to be alniost ineffective against the same tumour in the susceptible parent strain.In the following experiments, the curative dose for the C3H mammary carcinoma growing in reciprocal F, hybrids derived from high mammary tumour C3H strain and low-tumour strain mice is determined. All individuals of the F, generation are susceptible to transplants of the parent strain tumour and show no spontaneous regressions, yet the relative genetic incompatibility of this host tumo-tir relationship should, if radiosensitivity is dependent on host-resistance result in a significantly lower curative dose than that required by the same tumour in the parent strain.…”

“…Having established the median effective dose for the treatment of the C3H mammary adenocarcinoma in situ, it was subsequently demonstrated thatwhen the resistance of the tumourbearing animals was deranged by total-body irradiation, a significant decrease in the radiosensitivity of the tumour occurred (Cohen and Cohen, 1953a, 1953b (1940) showed that F2 hybrids, a cross between low-tumour and high-tumoiir mouse strains, bearing a mammary carcinoma originating in the high-tumour parent stock, exhibited a natural resistance evidenced by a moderate incidence of of spontaneous regressions, and were readily cured with a relatively small dose of radiation known to be alniost ineffective against the same tumour in the susceptible parent strain.…”