Inhibition of artificial and spontaneous lung metastases by preirradiation of abdomen--II. Target organ and mechanism.
We have previously reported that irradiation of the abdomen of mice before i.v. injection of both immunogenic and nonimmunogenic tumour cells is capable of suppressing their ability to form metastatic lung nodules in a time and dose-dependent fashion. Experiments with segmental exposure indicated the target organ to be located in the ventral half of the abdomen. The effect has now been shown positively to depend upon irradiation of the caecum, and can be abolished either by shielding the caecum from irradiation or by surgically removing it prior to irradiation. Further experiments have shown that the effect cannot be elicited in germ-free mice and that its magnitude is markedly reduced in animals given gut-sterilizing antibiotics. Split-dose irradiation only slightly reduced the magnitude of suppression, provided both doses were given within the time window of effectiveness of single doses. Tumour-growth retardation was observed and spontaneous lung metastases were also suppressed when tumour-bearing mice received abdominal irradiation 7 days after tumour cell transplantation into the leg. However, abdominal irradiation did not significantly reduce subsequent tumour transplantability by the s.c. or i.p. routes. The experimental data are consistent with a mechanism by which transmigration of enteric bacteria across the radiation-damaged mucous membrane of the caecum effectively results in an endogenous infusion of endotoxin.