Effect of difluoromethylornithine on chromosomes in living organisms and in tissue culture cells.

Abstract

DL-α-difluoromethylornithine (DFMO), a specific inhibitor of polyamine biosynthesis, has been shown to have antitumor and antitrypanosome effects. Significantly, our earlier work indicates that DFMO can also induce chromosome aberrations in Chinese hamster ovary (CHO) cells in serumfree medium, where extensive polyamine depletion can be achieved. We show now that DFMO increases chromosome aberrations in baby hamster kidney (BHK) cells, provided that effective polyamine depletion is ensured by growing the cells in low serum (0.2 %) medium. However. African green monkey kidney (Vero) cells cultured similarly in the low serum medium did not show enhanced chromosomal damage after DFMO treatment. DFMO did not induce chromosome aberrations in human lymphocytes, human fibroblasts or BHK cells grown in ordinary medium containing 10 % serum. Administration of DFMO to Chinese hamsters and to patients with lymphomas was not found to damage the chromosomes in peripheral lymphocytes andlor in bone marrow cells.