The effect of DES on bone marrow, 1982
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.
Diethylstilbestrol (DES) was formerly prescribed as a synthetic estrogen and also was used to fatten cattle. Human residues accumulated from ingestion of dairy and meat products have been found. Mice were exposed by subcutaneous injection to 0.2, 2 and 8 mg/kg body weight for 5 consecutive days. There was a dramatic decrease in marrow cellularity, CFU-S and CFU-GM (Table 1). These animals also exhibited highly enhanced sensitivity to Listeria monocytogenes and other generalized immunotoxic responses.
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.
- Full study (free access) : Assessment of myelotoxicity caused by environmental chemicals, Environmental health perspectives, NCBI PubMed, PMC1568900, 1982 Feb.