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Enhancement and Inhibition of Mammary Tumor Formation and Growth by Cytostatic Drugs¹

Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030

A group of cytostatic drugs used in the treatment of human breast cancer was injected into mice bearing preneoplastic, hyperplastic alveolar nodule outgrowth lines D2 and C4. The effects of melphalan, methotrexate, 5-fluorouracil, Cytoxan, vincristine, and prednisone on nodule growth, mammary tumor formation, and mammary tumor growth were examined in both lines. The results varied and depended on both the individual nodule lines and the drug. High doses of melphalan, Cytoxan, and 5-fluorouracil inhibited the rate of nodule growth in the mammary fat pads for both nodule lines. For nodule line D2, melphalan, 5-fluorouracil, Cytoxan, and vincristine enhanced and methotrexate and prednisone inhibited the rate of tumor formation. For nodule line C4, melphalan enhanced and 5-fluorouracil, Cytoxan, methotrexate, and prednisone inhibited the rate of tumor formation. Vincristine had no effect for line C4. There was no correlation between the effects on nodule growth and the rate of tumor formation for any of the drugs used in these experiments. In contrast, melphalan, 5-fluorouracil, Cytoxan, and methotrexate inhibited the growth of s.c. transplanted tumors derived from both nodule lines. These results suggest that preneoplastic mammary populations can respond differently from neoplastic mammary populations to the same cytostatic drugs, and that some cytostatic drugs can act to promote mammary tumorigenesis.

¹ Supported by Contract N01-CM-57018.

Received 4/11/77. Accepted 7/ 6/77.