EFFECTS OF CHEMOTHERAPEUTIC AND IMMUNOSUPPRESSIVE DRUGS ON THE PRODUCTION OF ERYTHROPOIETIN IN HUMAN HEPATOMA CULTURES

The effects of agents used in combination chemotherapy were studied on erythropoietin synthesis in cultures of the human hepatoma cell line, HepG2. Erythropoietin was measured by radioimmunoassay in the culture media after 24-h treatment periods. The RNA synthesis-inhibiting drugs daunorubicin, cyclophosphamide, ifosfamide, and cis-diamine-dichloroplatinum produced a dose-dependent decrease of the production of erythropoietin. Inhibition was also induced by the tubulin-binding agents vincristine and colchicine and the immunosuppressive agents azathioprine and cyclosporin A. The DNA synthesis-inhibiting drugs methotrexate and cytosine arabinoside, the antimycotics 5-fluorocytosine and amphotericin B, and glucocorticoids did not inhibit. Viability studies showed that the inhibition of erythropoietin production was partly correlated with cytotoxicity. These data could be relevant with respect to recombinant erythropoietin replacement therapy in tumor-associated anemia.