Accelerated Postirradiation Recovery of Hematopoietic Marrow Following Priming with Low Doses of Vincristine

Abstract

The present investigation is a continuation of efforts to characterize the radioprotective potential of priming with vincristine (VcR). In this study, the postirradiation recovery kinetics of the marrow's hematopoietic stem cell, progenitor cell, and stromal cell compartments were monitored following exposure to a range of sublethal radiation doses to determine (a) the optimal VcR/radiation intertreatment interval for achieving maximal hematopoietic protection, (b) whether this optimal interval is influenced by the dose of radiation administered, and (c) whether the radioprotection observed involves the hematopoietic stroma. The results demonstrate that the degree of radioprotection observed was significantly influenced by the scheduling of the VcR priming dose with respect to the radiation exposure. An intertreatment interval of 24 h provided maximal radioprotective benefit irrespective of the radiation dose administered. Additionally, the radioprotection following VcR priming appeared to be more the result of an accelerated recovery in the hematopoietic stem cell and progenitor cell compartments than a change in their intrinsic radiosensitivity. The data also suggest that this accelerated recovery was not a consequence of greater radioprotection of marrow stroma. Finally, the radioprotection observed following VcR priming did not appear to involve a selective lineage response by either the erythroid or the granulomonocytic progenitor compartments.

Natural Radioprotective Agents: An Overview

“…Vincristine affords protection to mouse against ionizing radiation and facilitates post-irradiation recovery of the hematopoietic cells [95]. Vinblastine enhances survival of irradiated mice by increasing their colony forming units [96].…”

Induction of Cell-Proliferation Hormesis and Cell-Survival Adaptive Response in Mouse Hematopoietic Cells by Whole-Body Low-Dose Radiation

“…CFU-GM and BFU-E were cultured by methylcellulose methods according to previously reported procedures (Johnke and Abernathy 1990;Real et al, 1992) with slight modifications. Bone marrow cells (1.0 ϫ 10 5 /ml for CFU-GM and 1.0 ϫ 10 6 /ml for BFU-E) were cultured in IMDM medium.…”

“…In addition, stimulation of the hematopoietic functions and protection of bone marrow from radiation were found in the animals pre-treated with other agents as compared to the animals without pretreatment. For example, certain toxic chemicals, such as protein-associated polysaccharides AM5 (Real et al, 1992), the anticancer drug vincristine [VCR, (Johnke and Abernathy 1990)], mild hyperthermia (Moroz et al, 1991) and metals (Soderberg et al, 1988), offered a marked protection from, or adaptive response to, radiation-induced hematopoietic depression. Pretreatment with low concentrations of AM5, VCR or mild hyperthermia stimulated and/or accelerated the recovery of the hematopoietic progenitor cells in the irradiated mice.…”

Accelerated marrow recovery following total‐body irradiation after treatment with vincristine, lithium or combined vincristine‐lithium

“…Priming with VcR one to two days prior to a lethal dose of irradiation has been demonstrated to markedly increase animal survival [6]-a response attributed to the ability of VcR to significantly accelerate recovery of critical hematopoietic stem cell populations as well as erythropoietic and granulopoietic progenitors [7-91. However, while radioprotection of the marrow microenvironment is also a key concern, priming with VcR has not been shown to accelerate recovery of the marrow stroma [9].…”