Lymphocyte stem cell alterations following perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Perinatal exposure of experimental animals to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to thymic atrophy and a suppression of cell-mediated immunity that is more severe and persistent than that caused by adult exposure, suggesting that events involved in the maturation of the immune system are particularly sensitive to TCDD. We report here that perinatal TCDD exposure produces an alteration in the lymphocyte stem cell population in the fetus and neonate, as evidenced by a significant reduction in the lymphocyte stem cell-specific enzyme terminal deoxynucleotidyl transferase (TdT). After maternal treatment with a single dose of TCDD (10 micrograms/kg of body weight) on gestational day (gd) 14, TdT biosynthesis and TdT-specific mRNA were reduced more than 50% in fetal liver lymphoid cells on gd 18. An even more extensive reduction was seen in neonatal bone marrow through postnatal day 18. In contrast, thymic TdT synthesis appeared to be relatively unaffected on a per cell basis by perinatal TCDD exposure, although the actual number of TdT-synthesizing thymocytes was diminished due to extensive thymic atrophy. These effects occurred at concentrations of 1-31 fg of TCDD/mg of thymus. Flow cytometric analysis of thymocyte surface marker expression revealed a slight decrease in the percentage of Lyt-2+L3T4+ thymocytes on gd 18 and postnatal day 4. This alteration was no longer apparent by postnatal day 11, when marrow TdT biosynthesis was most suppressed. These results suggest that TCDD-induced thymic atrophy during the perinatal period may be due, in part, to an effect on the prothymocyte.
Fine
J S
JS
Department of Biophysics, University of Rochester School of Medicine, New York 14642.
Gasiewicz
T A
TA
Silverstone
A E
AE
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001284:Atrophy; D004253:DNA Nucleotidylexotransferase / Q000235:genetics; D004147:Dioxins / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects*; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology
D000954:Antigens, Surface; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D004253:DNA Nucleotidylexotransferase