Proliferative state of normal in vitro colony-forming cells during development of L5222 rat leukemia and their reaction to chemotherapy

Abstract

In the experimental rat leukemia, L5222, the decrease of normal in vitro colony-forming cells (CFU-C) after chemotherapy with daunomycin is much less than in nonleukemic controls. The leukemia is therefore used here to test the hypothesis that in leukemia the CFU-C are expelled from the active cell cycle to a resting state and are thereby less sensitive to cycle-dependent chemotherapeutic agents. The L5222 leukemia has the advantage that the leukemic blast cells do not form colonies in agar culture so that normal CFU-C can be assessed under leukemic conditions. To compare the proportions of CFU-C in the S-phase in normal and leukemic rats, two S-phase-specific agents, 3H-thymidine and hydroxyurea, were used to kill proliferating bone marrow cells. Following treatment with 3H-thymidine in vitro, about 41% of the CFU-C were killed in normal and about 25% in leukemic bone marrow. Hydroxyurea administered in vivo resulted in the death of about 33% and 26%, respectively. The results indicate that fewer normal CFU-C are in S-phase in the L5222 leukemia, which might help to explain how enough normal stem cells survive chemotherapy to regenerate the bone marrow.

Relative effectiveness of methods for immunizing BALB/cwm mice to transplantable myelomonocytic leukemia

“…Transplantation models of the disease have been confined largely to the rat. The model of myelomonocytic leukemia (L5222) in syngeneic BDIX rats described by Hoelzer [11] is a particularly acute disease (102 leukemic cells are lethal in 12-13 days) and has been used primarily for pharmokinetic studies [9]. The transplantable "myeloblastic leukemia" in Donryu rats described by Aoshima and Ishidate [1] also is highly malignant (103 leukemic cells are lethal in 13-18 days).…”