Effect of pretreatment with cyclophosphamide on high-dose toxicity of melphalan in mice.
This study was undertaken to evaluate the effect of pretreatment (or priming) with cyclophosphamide (CY) on lethal toxicity of high-dose melphalan (MELPH) in mice. In C57BL/6 X DBA/2 F1 (hereafter called B6D2F1) mice given an injection of a single dose of CY, 50 mg/kg, 1-5 days before MELPH, 20 mg/kg, improved survival was noted in only one of five experiments. Reducing the challenge dose of MELPH to 17 mg/kg did not improve survival consistently. Priming with CY, 50 mg/kg, 3 days before a dose of MELPH, 20 mg/kg, did not improve survival in CBA/J or C57BL/6 mice. These results indicate that CY is an inconsistent priming agent for abrogating high-dose MELPH toxicity in mice. A slightly earlier recovery of regenerating hemopoietic and of jejunal crypt cells was noted in CY-primed B6D2F1 mice given injections of a low dose of MELPH, 15 mg/kg. The occasional improved animal survival noted in CY-primed B6D2F1 mice might be related to this earlier cell recovery.
D000818:Animals; D016026:Bone Marrow Transplantation; D003520:Cyclophosphamide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006410:Hematopoiesis / Q000187:drug effects; D007422:Intestines / Q000187:drug effects; D008297:Male; D008558:Melphalan / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA
D003520:Cyclophosphamide; D008558:Melphalan