ALTERATIONS IN MURINE FETAL THYMUS AND LIVER HEMATOPOIETIC-CELL POPULATIONS FOLLOWING DEVELOPMENTAL EXPOSURE TO 7,12-DIMETHYLBENZ[A]ANTHRACENE

Gestational exposure of ICR mice to the environmental contaminant 7, 1 2-dimethylbenz[a]anthracene (DMBA) was used (i) to study the developme ntal immunotoxicity of this chemical agent and (ii) to evaluate potent ial hematopoietic cellular targets in a sensitive developmental model which may be involved in immunosuppression induced by this carcinogeni c polycyclic aromatic hydrocarbon (PAH). DMBA produced a dose-dependen t hypocellularity in both fetal mouse thymus and liver. Resident hemat opoietic cell subpopulations in fetal liver, identified by CD44, CD45R , and Mac-1 monoclonal antibody binding, were reduced by the gestation al DMBA treatment. In particular, the total number of CD45R(+) B-linea ge lymphocytic cells in fetal liver was reduced to 20% of control leve ls by DMBA. Unlike previous reports with related PAH, DMBA did not inh ibit thymocyte differentiation, as indicated by unaltered thymocyte ex pression of CD4, CD8, and heat-stable antigens. These data may indicat e that production of thymic atrophy and impairment of thymocyte differ entiation by PAH involve separate mechanisms of action. Results of the present study additionally identify changes in immune cell population s that correlate well with inhibition of cell- and humoral-mediated im munity in experimental animals treated with DMBA. (C) 1995 Academic Pr ess, Inc.