Induction of marrow hypoxia by radioprotective agents.
The ability of thiol and non-thiol radioprotectors to induce hypoxia was determined using the binding of [3H]misonidazole by bone marrow cells as a measure of hypoxia. When administered at maximally radioprotective doses, four drugs (WR-2721, cysteamine, 5-hydroxytryptamine, and 16,16-dimethyl prostaglandin E2) significantly increased the amount of [3H]misonidazole bound by marrow cells, while no significant increase in binding was observed with three other agents (endotoxin, AET, superoxide dimutase). Doses of WR-2721 previously shown to provide suboptimal radioprotection did not significantly increase 3H-misonidazole binding. These results suggest that the physiological effects of some radioprotectors, that is, their ability to induce marrow hypoxia, may contribute to their efficacy in vivo.
Allalunis-Turner
M J
MJ
Cross Cancer Institute, Edmonton, Alberta, Canada.
Walden
T L
TL
Sawich
C
C
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D004999:Amifostine / Q000494:pharmacology; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells; D003543:Cysteamine / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010100:Oxygen / Q000378:metabolism*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D000338:beta-Aminoethyl Isothiourea / Q000494:pharmacology
D004731:Endotoxins; D011837:Radiation-Protective Agents; D000338:beta-Aminoethyl Isothiourea; D012701:Serotonin; D003543:Cysteamine; D013482:Superoxide Dismutase; D004999:Amifostine; D015064:16,16-Dimethylprostaglandin E2; D010100:Oxygen