This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Presant, C. A. Articles by Valeriote, F. Search for Related Content PubMed PubMed Citation Articles by Presant, C. A. Articles by Valeriote, F.

Kinetics of Both Leukemic and Normal Cell Population Reduction following 5-Azacytidine¹

Divisions of Hematology and Oncology, Department of Medicine at the Jewish Hospital of St. Louis [C. A. P.]; Mallinckrodt Department of Pediatrics, Division of Hematology and Oncology [T. V.]; and the Section of Cancer Biology, Division of Radiation Oncology, Department of Radiology [F. V.] Washington University School of Medicine, St. Louis, Missouri 63110

The cytotoxic effect of 5-azacytidine (AzaCR) on normal hematopoietic colony-forming units (NCFU) and L1210 leukemic colony-forming units (LCFU) in the femoral marrow of BALB/c x DBA/2 F₁ mice was studied using the spleen colony assay. Dose-survival curves for LCFU and NCFU were biphasic. Repopulation of LCFU was rapid at a low dose of AzaCR (0.1 mg/mouse) but was delayed for greater than 6 days at higher doses (0.25 mg/mouse and above). Of the agents tested in this system, only AzaCR exhibited these properties. Survival of mice with L1210 leukemia following AzaCR administration was prolonged beyond that predicted by the degree of LCFU reduction alone, and reflected the delay in LCFU repopulation. In contrast, repopulation of NCFU in normal mice was not delayed at a high dose of AzaCR (0.5 mg/mouse). AzaCR produced a nine-fold greater reduction of NCFU in leukemic mice than in normal mice, measured 5 days after AzaCR injection. While divided doses of AzaCR produced LCFU cytotoxicity equivalent to a single dose, 24-hr infusions of high doses were inferior to single injections.

¹ Supported by USPHS Grant CA 13053 and Contract CM-74-23 from the National Cancer Institute, and the Milton Moss Memorial Cancer Research Fund.

² To whom reprint requests should be addressed, at 216 S. Kingshighway, St. Louis, Mo. 63110.

Received 1/24/75. Accepted 4/14/75.