Decreased tolerance to dimethyl-myleran, cyclophosphamide and radiation in lymphoma-bearing mice.
A lethal dose of the cytotoxic agent dimethyl-myleran (DMM) is survived by 75-100% of mice reinfused with autologous bone marrow. In mice inoculated beforehand with a syngeneic Moloney lymphoma and then treated with lethal DMM, hemopoietic restoration and survival are compromised. With subcutaneous tumour challenge, in the face of substantial early toxicity, a therapeutic effect of DMM prevails. With intravenous or intraperitoneal tumour challenge the restorative potency of the autograft and thus the therapeutic drug effect are lost since practically all animals die from DMM. The reduced tolerance of mice carrying the Moloney lymphoma applies more generally to cytotoxic measures. The toxicity from sublethal doses of DMM, cyclophosphamide (CY) and total-body irradiation (TBI) is increased in mice inoculated subcutaneously shortly before with the lymphoma cells. The LD50 of the three agents is reduced by up to 70% according to the number of injected tumour cells or the time allowed for their multiplication. The effect is also provided by a cell-free tumour filtrate. Since the filtrate reduces bone marrow cellularity, the decreased tolerance could be due to the impairment of hemopoiesis by a tumour factor. Two human cancers growing as xenografts in immunosuppressed mice did not increase the sensitivity to DMM.
D000818:Animals; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007928:Lethal Dose 50; D008223:Lymphoma / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011836:Radiation Tolerance; D014916:Whole-Body Irradiation
C002037:dimethylmyleran; D003520:Cyclophosphamide; D002066:Busulfan