FETAL HEMATOPOIETIC ALTERATIONS AFTER MATERNAL EXPOSURE TO BENZO[A]PYRENE - A CYTOMETRIC EVALUATION

In utero exposure to the environmental contaminant benzo[a]pyrene (BaP ) was found to alter expression of murine thymocyte and liver fetal ce ll-surface markers. Pregnant mice were treated (via gavage) with 0, 50 , 100, or 150 mg BaP/kgld on gestational days (gd) 13-17, and offsprin g were examined on gd 18. Severe thymic atrophy and cellular depletion were found in BaP-exposed fetal mice. Flow cytometric analysis indica ted that the BaP treatment resulted in a significant decrease in the p ercentage of CD4(+)8(+) fetal thymocytes, as well as significantly inc reased CD4(-)8(-) and CD4(-)8(+) thymocytes. Staining of thymocytes wi th anti-mouse heat-stable antigen (HSA) and CD8 monoclonal antibodies produced similar results. These data suggest that BaP, in addition to producing thymic hypocellularity, inhibits normal thymocyte maturation processes. The BaP treatment was also found to decrease total fetal l iver cellularity including numbers of cells within resident hematopoie tic subpopulations. In particular, prolymphocytic cells, identified by CD44 and CD45R antigen expression and by presence oi nuclear terminal deoxynucleotidyl transferase (TdT), were significantly decreased in a nimals gestationally exposed to BaP. These data, taken together, indic ate that postnatal suppression of cell and humoral-mediated immune fun ction following in utero exposure to BaP may result from multiple targ eting of immune cells at different hematopoietic levels. Furthermore, results of the present study identify both qualitative and quantitativ e changes in fetal immune cell antigen expression that correlate well with the postnatal immunosuppression that occurs in experimental anima ls exposed to this carcinogenic polycyclic aromatic hydrocarbon.