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Protection against Late Effects of Radiation by S-2-(3-Aminopropylamino)-ethylphosphorothioic Acid¹

Biological and Medical Research Division [D. J. G., B. A. C., D. G.], Argonne National Laboratory, Argonne, Illinois 60439; Department of Radiation and Cellular Oncology [D. J. G.], University of Chicago, Chicago, Illinois 60637; and Radiation Oncology Department [C. P. S.], University of Louisville, Louisville, Kentucky 40202

We have demonstrated that S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR2721) administered to mice 30 min prior to a relatively low dose of ionizing radiation is effective in protecting against radiation-induced carcinogenesis and subsequent life shortening. Female C57BL/6JANL x BALB/cJANL F₁ mice, 200 per group, were exposed to gamma radiation at a dose of 206 cGy. Additional groups of 200 animals were sham treated, given injections of 400 mg/kg of WR2721, or administered WR2721 and the irradiated with ⁶⁰Co photons at doses of 206 cGy or 417 cGy. Mice were treated at 110 days of age. They were housed five to a cage and were checked daily throughout life. All deceased animals were necropsied, and tissues were removed and fixed for histopathological analysis. Over 90% of the animal deaths were due to tumor involvement. WR2721 afforded significant protection (P = 0.0016) against radiation-induced malignancies (i.e., a total of 164 tumor codes were used) following a dose of 206 cGy. Protection against lymphoreticular tumors in particular was significant (P = 0.0165). Subsequent survival time in WR2721-protected animals (compared with matched irradiated controls) was extended by 65 days. Mice irradiated with 417 cGy following administration of WR2721 exhibited a response similar to those irradiated without the protector at a dose of 206 cGy (P = 0.26). Cumulative survival curves for unirradiated mice were unaffected by a single dose of WR2721. These data indicate a potential novel benefit for radioprotectors in cancer therapy. WR2721 and similar aminothiols may be effective adjuvants for reducing the risk of therapy-induced secondary cancers in patients who have an excellent prognosis for cure and long-term survival.

¹ This investigation was supported by the U.S. Department of Energy under Contract W-31-109-ENG-38, by NIH/National Cancer Institute Grant CA-37435, and by the Center for Radiation Therapy.

² To whom requests for reprints should be addressed.

Received 2/13/91. Accepted 5/31/91.

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