Radiation protection of rat parenchymal hepatocytes with S-2-(3-aminopropylamino)ethylphosphorothioic acid.
The ability to protect parenchymal hepatocytes from ionizing radiation damage with S-2-(3-aminopropylamino)-ethylphosphorothioic acid (WR-2721) was investigated. The clonogenic survival of irradiated hepatocytes was determined with an in vivo transplantation assay system. Injection of WR-2721 (400 mg/kg) immediately after irradiation was without protective effect. In contrast, an intraperitoneal (IP) injection of WR-2721 30 min prior to 60Co irradiation resulted in a significant protection of parenchymal hepatocytes. The mean lethal dose (Do) and extrapolation number (n) of the survival curve for unprotected hepatocytes as 2.9 Gy and 1.8, respectively. The Do and n values for hepatocytes protected with WR-2721 were 5.7 Gy and 1.8, respectively. Thus, WR-2721 at a concentration of 400 mg/kg acted as a dose modifying agent with a dose modifying factor of approximately 2.0. Decreasing the concentration of WR-2721 to 200 mg/kg did not significantly reduce the radioprotective effectiveness of the drug. However, at concentrations less than 200 mg/kg, the radioprotective effect decreased in a dose-response manner with a concentration of 150 mg/kg providing 50% of the maximum effect observed.
D004999:Amifostine / Q000008:administration & dosage*; D000818:Animals; D002470:Cell Survival / Q000528:radiation effects; D003037:Cobalt Radioisotopes; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D008099:Liver / Q000528:radiation effects*; D009946:Organothiophosphorus Compounds / Q000008:administration & dosage*; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents; D051381:Rats; D011916:Rats, Inbred F344
D003037:Cobalt Radioisotopes; D009946:Organothiophosphorus Compounds; D011837:Radiation-Protective Agents; D004999:Amifostine