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Effects of Folate Deficiency on the Metastatic Potential of Murine Melanoma Cells^{1 ,2}

Departments of Medicine [R. F. B., C. A. P.], Pharmacology [J. J. M.], and Neurology [S. H. R.], and the Vermont Regional Cancer Center [L. A. M.], University of Vermont, Burlington, Vermont 05405

Experiments were designed to measure the effect of folic acid deficiency on a major determinant of cancer lethality, the propensity to form metastases. Murine B16 melanoma cells (F10 strain) were grown in folate-deficient and -supplemented media. After 3 days, cells in the deficient medium had restricted proliferative capacity, low folate levels by bioassay, increased cell volume, abnormal deoxyuridine suppression tests, accumulation of cells in S phase by flow cytometry, and increased numbers of DNA strand breaks. These folate-deficient cells consistently initiated more pulmonary metastases than control cells when injected into host mice. Cell size did not appear to be a major factor in pulmonary metastasis formation. In vitro growth rates and cloning efficiencies were comparable for cells in both types of medium as was subcutaneous growth of tumors. We conclude that folate deficiency increases the metastatic potential of cultured melanoma cells.

¹ This work was supported by grants from the Vermont Division of the American Cancer Society, the National Cancer Institute (CA 24543, CA 41843, and 1S10 RRO 1510-01), and the American Institute for Cancer Research. Presented in part at the national meeting of the American Society of Clinical Investigation, May 1985 (31).

² Recipient of a Research Career Development Award from the NIH (CA-00946). To whom requests for reprints should be addressed, at Hematology/Oncology Unit, 32 N. Prospect Street, University of Vermont, Burlington, VT 05405.

³ Supported by a grant from the Sandoz Foundation of America.

Received 1/11/88. Revised 5/12/88. Accepted 5/19/88.

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