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Selective Protection of the Gastrointestinal Tract against Radiation Injury by Perfusion with MEG (2-Mercaptoethylguanidine Hydrobromide)^1,2,

( Roswell Park Memorial Institute and the State University of New York at Buffalo, Buffalo, New York)

A procedure was developed for perfusing the gastrointestinal tract of rats with solutions of MEG, the active metabolite of 2-aminoethylisothiouronium (AET), during whole-body irradiation. In Fischer 344 rats, whole-body irradiation with 900 r was found to kill all animals by producing intestinal injury within 1 week, before hemopoietic depression could fully develop. Transplantation of isologous bone marrow did not protect against such doses of radiation. Whole-body irradiation with 900 r was survived by 19 of 20 animals when the gastrointestinal tract was perfused with MEG during irradiation and isologous bone marrow transplantation was performed after irradiation. This procedure showed some protection against whole-body irradiation with 1200 r and possibly 1500 r, but all animals succumbed after 1800 r.

Single whole-body irradiation with 900 r combined with intestinal protection and bone marrow transplantation failed to eradicate disseminated transplanted Dunning leukemia IRC 741. To determine the radiation sensitivity of Dunning leukemia cells, subcutaneous implants were irradiated 24 hr after implantation, the rest of the animal being protected with lead shielding. It appears that doses in excess of 5000 r are required in order to eradicate this tumor. If the Dunning IRC 741 leukemia can be considered representative of diseases of the lymphoma-leukemia group, it is not likely that the procedure outlined will allow selective radiation therapy of disseminated hematologic malignancy with whole-body irradiation, because of the high radiation doses needed. It is conceivable, however, that filling intestinal loops in the irradiation field with MEG solutions may permit delivery of higher doses of local radiation to radiation-responsive abdominal tumors (e.g., lymphosarcoma) than are allowable at the present time.

¹ Supported by USPHS research grant RH-00026, Division of Radiological Health, and USPHS research grant CA-04487, National Cancer Institute.

² Preliminary reports of some of the experiments included in this study were presented at the annual meetings of the American Association for Cancer Research in 1958 (2) and 1961 (1).

Received 11/23/64.