Radiobiological evaluation of a newly synthesized cysteamine derivative.
A new cysteamine-based compound, I109 (N-glycylglycyl-S acetylcysteamine trifluoroacetate) was tested on both normal tissues and tumors to evaluate its radioprotective potential. I109, which is three times less toxic than WR-2721, was injected at a dose approximately equal to half the LD50(30 days). The Protection Factor (PF = gamma ray dose ratio) after whole body irradiation was 1.3-1.4 for intestinal death and 1.4-1.5 for hemopoietic death when intervals of 40 or 20 min elapsed between injection and the end of irradiation. A crypt cell assay was done for both I109 and WR-2721; PFs were 1.1 and 1.4, respectively. I109 was then tested on five solid tumors. For each cell line (4 human, 1 murine) one dose of radiation was delivered. Surviving fraction ratios with and without drug ranged between 2.4 and 14.1 when an interval of 20 min elapsed between injection and the end of irradiation. The degree of radioprotection proved time dependent for EMT6 and HRT18; radioprotection afforded by WR-2721 on these tumors is either similar or greater than radioprotection afforded by I109 depending on the time interval between injection and irradiation.
D004999:Amifostine / Q000627:therapeutic use; D000818:Animals; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000532:radiotherapy*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*
D011837:Radiation-Protective Agents; D003543:Cysteamine; C050088:N-glycylglycyl-S-acetylcysteamine trifluoroacetate; D004999:Amifostine