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Erythropoietin-induced Polycythemia in Athymic Mice following Transplantation of a Human Renal Carcinoma Cell Line¹

The Liver Unit, Department of Medicine A, Hadassah University Hospital, Jerusalem, Israel 91120 [D. S., M. A., E. G.], and Division of Hematology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461 [J. B. S.]

An established cloned human renal carcinoma line RC-1, which has been continuously maintained in culture for several years and which produces erythropoietin, was injected s.c. into BALB/c athymic mice and produced tumors. Tumorigenicity was directly correlated with the number of RC-1 cells inoculated. Tumor cell histology resembled the original patient-derived tumor. Tumor-bearing mice developed hepatosplenomegaly and significant reticulocytosis with elevated hemoglobin and hematocrit values that were proportional to tumor mass. In addition, red cell mass and blood volume of nude mice increased over 100% as compared to control mice or to animals bearing nonrelevant neoplasms. Large amounts of immunoreactive erythropoietin could be extracted from the nude mouse RC-1 tumors. These results indicate that the RC-1 cell line is tumorigenic and produces biologically active erythropoietin in vivo in athymic mouse hosts, thus providing a reproducible model to study ectopic erythropoietin production and its regulation in vivo.

¹ Supported by a grant from the Richard Molin Research Foundation for Cancer Research and by Genetics Institute, Boston, MA.

² To whom requests for reprints should be addressed, at Division of Hematology, Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461.

Received 8/11/87. Revised 1/13/88. Accepted 3/17/88.

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