WR-2721, its derivatives and their radioprotective effects on mammalian cells in culture.
Although it is well known that WR-2721 is very efficient in protecting mice against lethal irradiation, we could not find any radioprotective effect of WR-2721 on mouse L cells in culture. But WR-1065 alone (free SH form of WR-2721), and WR-2721 pre-incubated with mouse liver homogenate, showed radioprotective ability. It was found that mouse liver homogenate dephosphorylated WR-2721 to WR-1065. The highest WR-2721 metabolizing activity was found in mouse liver homogenate and Chang liver cell homogenate. Homogenates of human liver and kidney were also shown to possess moderate activity for metabolizing WR-2721. These results suggest to us that WR-2721 must be dephosphorylated before exerting its radioprotective effect and that this dephosphorylating activity varies with tissues. It is demonstrated therefore that mouse L cell in culture is a novel system to assess the extent of dephosphorylation of WR-2721 in various tissues.
D000368:Aged; D004999:Amifostine / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D007739:L Cells / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008624:Mercaptoethylamines / Q000494:pharmacology*; D051379:Mice; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*
D008624:Mercaptoethylamines; D009946:Organothiophosphorus Compounds; D011837:Radiation-Protective Agents; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D004999:Amifostine