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The halogenated aromatic hydrocarbon, 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD), is a ubiquitous, highly toxic environmental contaminant shown to produce immunotoxic effects in mammals. Although its immunotoxicity has been widely reported, little is known regarding its effect upon the development of immune-system cells, especially the B lymphocyte. The present study's purpose was to assess the effect that a single-dose administration of TCDD has, over time, upon bone marrow B-cell progenitors and pro/pre-B-, immature B-, and mature B-cell subpopulations, and to establish a dose-response relationship for these changes. Results showed that the mature B-lymphocyte subpopulation varied in a time-dependent manner, with a significant increase one day following TCDD treatment (30 microg/kg body weight [bw]), followed by a significant decrease at day 9 and a return to near-vehicle levels by day 31. Developing and less mature subpopulations were significantly decreased at days 6 and 9. The earliest B cell-progenitor subpopulation increased until day 9 and then decreased to vehicle-treated levels. Dose response (30, 15, 9, 6, 3, and 0.3 microg TCDD/kg bw) results at 2 days following treatment showed that only the mature-B subpopulation was affected at these doses, and below 6 microg/kg bw no effect was observed. These data suggest that the primary effect of TCDD is on those cells entering, and/or within, the mature B-lymphocyte subpopulation, and the alteration observed in the earlier maturation stages is a compensatory response to the effect on these mature cells.

toxicological sciences

A Single Dose of 2,3,7,8-Tetrachlorodibenzo-p-dioxin Produces a Time- and Dose-Dependent Alteration in the Murine Bone Marrow B-Lymphocyte Maturation Profile