Abstract
CBA mice inoculated ip with Ehrlich ascites carcinoma (EAC) cells were later inoculated with various doses of cyclophosphamide (CY) iv (120–300 mg/kg). The survival time of mice was shortened when CY was given 2 or 11 days after EAC inoculation and prolonged when CY was given 5 or 7 days after EAC inoculation. The decline of cellularity in the spleen and the lymph node after injection of a sublethal dose of 180 mg CY/kg, expressed as the number or fraction of surviving cells, was the greatest in mice given CY 2 days after EAC. In mice given CY 5 or more days after EAC, the number of cells surviving was similar to that in normal mice treated with CY. However, due to increased initial cellularity, the fraction of surviving cells was lower in tumor-bearing animals. The resistance to tumor of mice immunized with an injection of X-irradiated EAC cells was suppressed completely if 180 mg CY/kg was given 2 days after immunization and only partially if the same dose of CY was given after 5 or more days. Administration of CY was lethal in the former mice even without tumor challenge. Intensified destruction of the host's lymphoid tissue was determined to be responsible for the noxious effect of CY in mice with initial tumors. The beneficial effect of CY in mice with medium-sized tumors was most probably due to its prevalent tumoricidal action. The noxious effect of CY in mice with advanced tumors remained to be clarified.
Published Version
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