Radiobiology of the C3H Mouse Mammary Carcinoma: Increased Radiosensitivity of the Tumour Induced by Inoculation of the Host with Radiation-Attenuated Isografts

Abstract

IN a previous communication (Cohen and Cohen, 1954b) it was noted that tumours arising from viable grafts of the C3H mammary carcinoma, which had been attenuated by sublethal doses of radiation immediately before implantation, were found, when subsequently irradiated in situ, to have a significantly increased radiosensitivity. The radiosensitization did not appear to be due to any permanent change in the tumour, or to any local reaction in the tumour bed, but could be explained only on the basis of a subliminal systemic resistance mechanism, possibly in the nature of a circulating iso-antibody arising in the host. If this postulate is correct, it might be possible to enhance the radio-sensitivity of an established non-attenuated isograft by inoculation of the host with a suitably attenuated second implant. The present investigation demonstrates that induced radiosensitization of an isogenic tumour in inbred mice is feasible, and may possibly point the way to more efficient therapy of autogenous growths.The procedure is complicated by additional variables not encountered when the radiation-attenuated homografts themselves are treated. The attenuation doses can vary widely, and may include a higher dosage range where the irradiated inocula no longer "take ". One may also choose almost any interval between implantation of the unmodified tumour and the inoculation of the irradiated fragment. Further, the time between the dates of implantation of the attenuated inoculum and of the treatment in situ of the established tumour may vary widely. The present experiment, therefore, is designed firstly to explore the possibility of radiosensitization of an unmodified transplanted C3H mammary adenocarcinoma by means of an attenuated tumour inoculum, and secondly to seek effective combinations of timing and dosage factors for this type of procedure. MATERIALS AND METHODS Experimental designYoung adult male mice from the C3H/Cg substrain were used. Each received two inoculations: one consisting of fragments of an unmodified inoculum, that is the usual isogenic C3H mammary tumour homoplast, into the right flank, and the second an attenuated inoculum, tumour fragments irradiated in vitro prior to implantation, into the left flank. After a suitable period, depending on the experimental variables, the unmodified tumour was irradiated in situ using the standard procedure. It was considered that the following variables might affect

Adjuvant Therapy for Adenocarcinoma of the Kidney: Present Position and Prospects1

“…Thus, following nephrectomy and radiotherapy to the renal bed and para-aortic nodes, specific active immunotherapy using a vaccine prepared from the patient's own irradiated tumour or, alternatively, specific adoptive immunotherapy with sensitised lymphocytes, may prove more effective in destroying residual malignant cells than irradiation alone. Cohen and Cohen (1956) and also Haddow and Alexander (1 964) reported an increased response to irradiation of experimental tumours following injections of irradiated tumour autograft. This might be explained by the destruction, through immunological mechanisms, of residual cells after eradication of the main tumour mass by conventional treatment.…”

The combined effect of radiotherapy and neuraminidase‐treated tumor cells on 3‐methylcholanthrene‐induced fibrosarcoma

“…Cohen (1960),Powerset al (1967) and Suit and Kastelan (1970) showed that the radiation dose required for local tumor control was increased when animals were imniunosuppressed. Conversely, tumors growing in preimmunized animals were more easily cured by local radiotherapy (Cohen and Cohen, 1956;Suit and Kastelan, 1970). The mechanism by which irradiation may augment the normal degree of tumor immunity possessed by animals bearing small tumors is not known.…”

Tumour-cell killing by X-rays and immunity quantitated in a mouse model system

“…THERE are well documented studies which show that host factors in the mouse are important determinants of tumour radiosensitivity (Cohen & Cohen, 1956;Haddow & Alexander, 1964;Powers et al, 1967;Maruyama, 1967;Suit & Kastelan, 1970). However, the biological mechanism which effects this improved response is not clearly understood (Song & Levitt, 1975;Johnson, 1978).…”