Adult rats were given 10(5) or 10(6) Yoshida
ascites sarcoma (YAS) cells IP and were treated with
cyclophosphamide (CY) given IP in single doses of 20 mg/kg or 100 mg/kg, 2 or 5 days after YAS inoculation. Both the curative effect of CY and subsequent resistance to
tumor challenge in rats that survived depended on the dose of injected
tumor cells and on the dose and time of administration of CY. These three factors determined whether the host's immune response to
tumor antigens would develop and contribute to the overall anti-
tumor effects of the
chemotherapy. The curative effects of CY were significantly less pronounced in T-cell-deficient than in normal rats. Anti-
tumor and immunosuppressive activities of CY exerted opposite influences on the ultimate result of the
chemotherapy. Adverse immunosuppressive effects prevailed when the
drug was administered early (2 days) after YAS inoculation. In this case the
chemotherapy was less efficient and the surviving rats were susceptible to a subsequent
tumor challenge. Further analysis showed that the injection of CY 2 days after inoculation of YAS
antigens induced strong and specific immunologic tolerance to the
tumor. In contrast, when a sufficient amount of
tumor antigens (higher dose of
tumor cells injected and CY injection delayed) elicited an anti-YAS immune response that was not suppressed by early injection of CY (CY administered 5 days after the
tumor) effective eradication of
tumor cells and anti-YAS resistance in cured animals were observed.