Radioprotection of hematopoietic tissues in mice by indomethacin.
We recently reported that indomethacin, an inhibitor of prostaglandin (PG) synthesis, increased the radioresponse of PG-producing murine tumors, but it protected the hematopoietic system from radiation damage [Furuta et al., Cancer Res. 48, 3008-3013 (1988)]. Here we have investigated possible mechanisms responsible for the radioprotective effect of indomethacin. In the exogenous spleen colony assay, bone marrow cells from indomethacin-treated mice showed a similar radioresponse to those from mice not treated with indomethacin, thus excluding true radioprotection as a mechanism. Also, neither the total number of bone marrow cells nor the number of stem cells in bone marrow were affected by the treatment with indomethacin. However, indomethacin induced significant splenomegaly, which was associated with an increased number of both nucleated cells and hematopoietic stem cells in the spleen. The latter was determined by the exogenous spleen colony assay. Thus indomethacin protected hematopoietic tissue indirectly through stimulation of hematopoietic cells in the spleen. When indomethacin was combined with WR-2721, which is a true radioprotector, we obtained a greater radioprotective effect than with either used alone according to the endogenous spleen colony assay.
Nishiguchi
I
I
Department of Experimental Radiotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Furuta
Y
Y
Hunter
N
N
Murray
D
D
Milas
L
L
D004999:Amifostine / Q000627:therapeutic use; D000818:Animals; D004357:Drug Synergism; D005260:Female; D006413:Hematopoietic System / Q000187:drug effects* / Q000528:radiation effects; D007213:Indomethacin / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D011837:Radiation-Protective Agents / Q000627:therapeutic use*
D011837:Radiation-Protective Agents; D004999:Amifostine; D007213:Indomethacin