Assessment of myelotoxicity caused by environmental chemicals.
Potential antineoplastic agents must be screened for the delayed toxicity that occurs in many cases of drug-induced bone marrow aplasia. In vitro clonal assays for hematopoietic progenitor cells have been developed to assess the degree of myelotoxicity. This adverse side effect is often the limiting factor in the development of new cancer chemotherapeutics. In addition, many environmental chemicals are cytotoxic to rapidly proliferating cells, but a systematic assessment of their myelotoxicity has not been performed. We have used clonal marrow assays to investigate a panel of chemicals including 2,3,7,8-tetrachlorodibenzo-p-dioxin, polybrominated biphenyls, diethylstilbestrol, benzo(a)pyrene and indomethacin. All were immunotoxic, some to pleuripotent hemopoetic stem cells and other to granulocyte-macrophage progenitors, and at concentrations below those causing other toxic manifestations. This shows that these bone marrow clonal assays, and hopefully future one for erythroid, B- and T-lymphocytes, and megakaryocytes, will provide the specificity and sensitivity necessary to delineate the myelotoxicity of a broad spectrum of environmental chemicals.
D000818:Animals; D001580:Benzopyrenes / Q000633:toxicity; D001853:Bone Marrow / Q000187:drug effects*; D004054:Diethylstilbestrol / Q000633:toxicity; D004785:Environmental Pollutants / Q000633:toxicity*; D004920:Erythropoiesis / Q000187:drug effects; D005260:Female; D006098:Granulocytes / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D011075:Polybrominated Biphenyls / Q000633:toxicity; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity
D001580:Benzopyrenes; D004785:Environmental Pollutants; D011075:Polybrominated Biphenyls; D000072317:Polychlorinated Dibenzodioxins; D004054:Diethylstilbestrol