Protection of murine bone marrow by dexamethasone during cytotoxic
chemotherapy
AB Kriegler, D Bernardo and SM Verschoor
Cell Biology Unit, Peter MacCallum Cancer Institute, Melbourne, Victoria,
Australia.
Corticosteroids have the ability to suppress the production of growth
factors and cytokines and are thus implicated in the negative regulation of
hematopoiesis. We have shown that the corticosteroids, prednisolone and
dexamethasone, were able to effectively protect progenitor cells in four
strains of mice against cell-cycle-specific antimetabolic chemotherapy
agents. The highest levels of protection against 5-fluorouracil (FU; 200
mg/kg) were achieved when two or three intraperitoneal injections of
dexamethasone were administered between - 7 and +3 hours at a dose of 7.5
mg/kg/injection (optimal dose) or by continuous infusion between -4 and +20
hours. This protective effect is manifested as an increase in the number of
high proliferative potential colony-forming cells that survive in the bone
marrow 3 days after treatment with FU from between 0.5% and 11% to between
10% and 34% of normal. The bone marrow progenitors and blood cell numbers
return to normal from 3 to 5 days and 1 to 2 days earlier, respectively.
Less dexamethasone than prednisolone is required to give an equivalent
protective effect, which is consistent with their anti-inflammatory
potency. These findings are further evidence of the negative regulatory
role played by corticosteroids, and indicate that the treatment schedules
of corticosteroids during cancer therapy need to be reexamined to obtain
the maximum benefit from their use.
Volume 83,
Issue 1,
pp. 65-71,
01/01/1994
Copyright © 1994 by The American Society of Hematology
