Suppression of bone marrow stromal cell function by benzene and hydroquinone is ameliorated by indomethacin.
Administration of benzene to mice will inhibit bone marrow stromal cell-supported hemopoiesis in culture. Hydroquinone, a major metabolite of benzene, will cause a similar inhibition of stromal cell function in vitro. Stromal cells produce both an inducer (colony-stimulating factor) and an inhibitor (prostaglandin E2; PGE2) of hemopoiesis. This research was conducted to determine if prostaglandin synthesis is involved in the suppression of stromal cell function by benzene and hydroquinone. Male B6C3F1 mice were administered benzene (100 mg/kg), indomethacin (1 mg/kg), or benzene plus indomethacin twice a day for 4 consecutive days. On Day 5 bone marrow cells were removed to determine the effect of treatment. In a second series of experiments mouse bone marrow stromal cells in culture were treated with hydroquinone (10(-7) to 10(-4) M), indomethacin (10(-6) M), or a combination of hydroquinone plus indomethacin. Stromal cell function was based on the ability of the treated stromal cells to support granulocyte/monocyte colony development in coculture. The results demonstrated that preadministration of indomethacin in vivo ameliorated benzene-induced inhibition of bone marrow stromal cell function. In vitro, indomethacin ameliorated hydroquinone toxicity to stromal cell function. Benzene administration in vivo induced elevated PGE2 in bone marrow samples which were prevented by preadministration of indomethacin. However, hydroquinone in vitro did not induce a consistent increase in PGE2 levels. These results suggested that toxicity to stromal cells was not due solely to increased prostaglandin synthetase activity.
D000818:Animals; D001554:Benzene / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001853:Bone Marrow / Q000032:analysis / Q000187:drug effects*; D002478:Cells, Cultured; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006873:Hydroquinones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011458:Prostaglandins E / Q000032:analysis
D006873:Hydroquinones; D011458:Prostaglandins E; D011451:Prostaglandin-Endoperoxide Synthases; D001554:Benzene; D015232:Dinoprostone; C031927:hydroquinone; D007213:Indomethacin