Protection against late effects of radiation by S-2-(3-aminopropylamino)-ethylphosphorothioic acid.
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.
Grdina
D J
DJ
Biological and Medical Research Division, Argonne National Laboratory, Illinois 60439.
Carnes
B A
BA
Grahn
D
D
Sigdestad
C P
CP
D004999:Amifostine / Q000627:therapeutic use*; D000818:Animals; D003037:Cobalt Radioisotopes; D005260:Female; D005720:Gamma Rays; D051379:Mice; D008815:Mice, Inbred Strains; D009381:Neoplasms, Radiation-Induced / Q000473:pathology / Q000517:prevention & control*; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D012016:Reference Values; D013997:Time Factors
D003037:Cobalt Radioisotopes; D004999:Amifostine