Modulation of radioprotective effects of respiratory hypoxia by changing the duration of hypoxia before irradiation and by combining hypoxia and administration of hemopoiesis-stimulating agents.
OBJECTIVE
Analysis of radioprotective effect of respiratory hypoxia on hemopoietic tissue and enhancement of this effect by hemopoietic activation.


METHODS
In mice breathing hypoxic gas mixture during total body gamma irradiation the recovery of pluripotent and committed granulocyte-macrophage progenitor cells and animal lethality were determined.


RESULTS
In mice forced to breathe 10% O2 and 8% O2 during irradiation, the oxygen tension in the spleen decreased to 40% and 20%, respectively, of control values. Hypoxia mitigated the lethal effect of gamma-rays and improved the recovery of hemopoiesis in compartments of pluripotent and committed progenitor cells. Enhancement of the proliferative activity in hemopoietic tissue by a cytokine (rmGM-CSF) or an immunomodulator (dextran sulfate) increased the effect of hypoxic radioprotection, while elimination of proliferative cells by hydroxyurea decreased the radioprotective effect. Adaptation of experimental animals to hypoxic conditions was found to reduce the radioprotective effect without influencing tissue partial oxygen pressure lowered by hypoxic conditions.


CONCLUSIONS
The data presented confirm the radioprotective effect of 10% and 8% O2 respiratory hypoxia on hemopoiesis. These findings may represent a way out for further experimental and clinical research aimed at considering differential protection of various tissues by hypoxia.
Vacek
A
A
Institute of Biophysics, Academy of Sciences of Czech Republic, Brno, Czech Republic. vacek@ibp.cz
Tacev
T
T
Hofer
M
M
D000222:Adaptation, Physiological; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D003037:Cobalt Radioisotopes / Q000008:administration & dosage; D016264:Dextran Sulfate / Q000494:pharmacology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D006918:Hydroxyurea / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009374:Neoplasms, Experimental / Q000401:mortality / Q000503:physiopathology*; D009381:Neoplasms, Radiation-Induced / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control*; D010100:Oxygen / Q000378:metabolism; D011829:Radiation Dosage; D011994:Recombinant Proteins; D013154:Spleen / Q000378:metabolism; D013997:Time Factors; D014916:Whole-Body Irradiation
D000970:Antineoplastic Agents; D003037:Cobalt Radioisotopes; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016264:Dextran Sulfate; D010100:Oxygen; D006918:Hydroxyurea