The antimetastatic effect of (±)-1,2-bis(3,5-dioxopiperazine-1-yl)propane (ICRF 159) on the Lewis lung carcinoma has been examined at tissue level. The effect has been compared with that of cyclophosphamide on the same tumor and with ICRF 159 on other tumors. Histological changes induced by ICRF 159 in the Lewis lung carcinoma tumor have been followed over a period of time. They lead to the conclusion that the antimetastatic activity of ICRF 159 is due to the striking changes that it induces in the morphology and physiology of the developing tumor vasculature with the result that their appearance and behavior resembles that of normal blood vessels. Malignant cells no longer line the tumor vascular channels and are also probably unable to enter the normalized tumor vessels. Blood-borne tumor dissemination is thereby prevented, but the propensity of the treated tumors for uncontrolled proliferation and invasion of adjacent tissues remains unimpaired.

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