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Effect of (±)-1,2-Bis(3,5-dioxopiperazin-1-yl)propane on Tumor Blood Vessels and Its Relationship to the Antimetastatic Effect in the Lewis Lung Carcinoma

Cancer Chemotherapy Department, Imperial Cancer Research Fund, Lincoln's Inn Fields, London, WC2A 3PX [S. E. J.], and Haematology Department, Brompton Hospital, Fulham Road, London, S.W. 3 [A. J. S.], England

(±)-1,2-Bis(3,5-dioxopiperazin-1-yl)propane in C57/BL female mice bearing the Lewis lung carcinoma inhibits metastases at doses that do not influence the growth of the primary implant. Variation of dose level and time of administration of the drug indicated that its antimitotic action did not contribute directly to its antimetastatic effect. Dose levels that gave highly significant inhibition of metastases produced profound vascular changes in the primary tumors. In the control and ineffectively treated tumors, the vessels were poorly formed sinusoidal channels lined with malignant cells, and frequent areas of hemorrhage were present. In contrast, tumors of treated mice with no evidence of metastatic growth had discreet, well-endothelialized blood vessels, and no hemorrhages were observed. These observations are compatible with the explanation that the antimetastatic effect is due to changes in the vasculature that prevent the entry of Lewis lung carcinoma cells into the circulation and hence their release from the primary tumor.

Received 9/10/73. Accepted 1/ 8/74.

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