The modification of melphalan toxicity in tumor bearing mice by s-2-(3-aminopropylamino)- ethylphosphorothioic acid (WR 2721).
The toxicity of melphalan in mice was reduced by the injection of S-2-(3-aminopropylamino)-ethylphosphorothioic acid (WR2721). This was seen in terms of reduced toxicity to the stem cells of the bone marrow and intestinal epithelium as well as improved animal survival. Using human melanoma xenografts and growth delay as an end-point, it was demonstrated that WR2721 did not protect this tumor from melphalan. With radio-labelled WR2721, it was shown that WR2721 was rapidly cleared from the blood and actively accumulated by all normal tissues except the CNS. Intact human tumor xenografts and Lewis lung tumors were less able to accumulate WR2721 than normal tissues, but in vitro studies showed that tissue fragments or single cell suspensions of tumors were as efficient as liver fragments or bone marrow cells in accumulating the drug. The rapid clearance of WR2721 and poor vascularity of the intact tumors were thought to be responsible for the differential uptake and protection of normal tissues by WR2721.
D004999:Amifostine / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D003114:Colony-Forming Units Assay; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D008297:Male; D008545:Melanoma / Q000032:analysis / Q000188:drug therapy; D008558:Melphalan / Q000633:toxicity*; D051379:Mice; D008808:Mice, Inbred CBA; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology
D009946:Organothiophosphorus Compounds; D004999:Amifostine; D008558:Melphalan