ALTERATIONS IN THE DEVELOPING IMMUNE-SYSTEM OF THE F344 RAT AFTER PERINATAL EXPOSURE TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN .2. EFFECTS ON THE PUP AND THE ADULT

Our recent work showed that in utero 2,3,7,8-tetrachlorodibenzo-p-diox in (TCDD) exposure produced alterations in fetal and neonatal thymocyt e subpopulations. This study was designed to determine the persistence and functional significance of these alterations. One group of timed- bred pregnant F344 rats was dosed with 3.0 mu g TCDD/kg by gavage on g estational day 14 (GD14). The immune function of the perinatally-expos ed offspring and age-marched controls were assessed at 14-17 weeks old . Examination of the organ weights and splenic phenotypes showed that TCDD exposure increased the spleen/body weight ratio, decreased the th ymus/body weight ratio, and decreased the percentage of splenic CD3(+) /CD4(-)CD8(-) cells in both genders. The delayed-type hypersensitivity (DTH) response to bovine serum albumin (BSA) was suppressed in both t he TCDD-exposed males and females. The lymphoproliferative (LP) respon ses to T-cell and B-cell mitogens and the antibody response to sheep r ed blood cells were not affected by perinatal TCDD exposure in either gender except for a suppressed LP response to PWM in the females. A se cond set of timed-pregnant F344 rats was dosed with 0 or 1.0 mu g TCDD /kg on GD14. One day after birth litters were cross-fostered to produc e control, placental-only, lactational-only, and placental/lactational exposure groups. The organ weights and thymic and splenic phenotypes of these pups were assayed 1, 2, or 3 weeks post-partum, while the DTH response was assessed in 5-month-old males. Increased liver/body weig ht ratios, decreased percentages of thymic CD3(+)/CD4(-)CD8(-) cells, and increased percentages of thymic CD3(+)/CD4(-)CD8(+) cells were see n through 3 weeks old in both genders after TCDD exposure. The severit y of the effects was related to the route of exposure (i.e. placental/ lactational > lactational > placental). The DTH response to BSA was su ppressed in the males receiving both placental and lactational exposur e. These results suggest that the immunotoxic effects of perinatal TCD D exposure of rats persist into adulthood and that suppression of the DTH response may represent the most sensitive biomarker for TCDD-induc ed immunotoxicity in this species. (C) 1997 Elsevier Science Ireland L td.