Dephosphorylation of WR-2721 with mouse tissue homogenates.
Mouse liver homogenate had an optimum pH of 8.6 to 8.8 for dephosphorylation of WR-2721 in the analyzed pH range from 5.2 to 10.0. At this optimum pH condition, the dephosphorylation activities of six mouse tissue homogenates were analyzed. Kidney, liver and small intestine homogenates showed higher dephosphorylation activities (935, 336 and 314 nmoles/mg protein/hr, respectively) than spleen and lung homogenates (86, 49 nmoles/mg protein/hr, respectively). Furthermore, serum did not show any dephosphorylation activity. The high activity found in liver homogenate agrees well with our previous data with mouse L cells. However, optimum pH from 8.6 to 8.8 in liver homogenate is quite different from the data reported by using Ehrlich ascites tumor cells (optimum pH was 5.6). Therefore, it is suggested that WR-2721 administered into mouse is efficiently dephosphorylated in certain tissues such as liver to its active form with the enzyme(s) different from that found in Ehrlich ascites tumor cells.
D004999:Amifostine / Q000097:blood / Q000378:metabolism*; D000818:Animals; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D009946:Organothiophosphorus Compounds / Q000378:metabolism*; D011837:Radiation-Protective Agents / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism
D009946:Organothiophosphorus Compounds; D011837:Radiation-Protective Agents; D004999:Amifostine