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 7,12-dimethylbenz[a]anthracene (DMBA) was used (i) to study the developmental immunotoxicity of this chemical agent and (ii) to evaluate potential hematopoietic cellular targets in a sensitive developmental model which may be involved in immunosuppression induced by this carcinogenic polycyclic aromatic hydrocarbon (PAH). DMBA produced a dose-dependent hypocellularity in both fetal mouse thymus and liver. Resident hematopoietic cell subpopulations in fetal liver, identified by CD44, CD45R, and Mac-1 monoclonal antibody binding, were reduced by the gestational DMBA treatment. In particular, the total number of CD45R+ B-lineage lymphocytic cells in fetal liver was reduced to 20% of control levels by DMBA. Unlike previous reports with related PAH, DMBA did not inhibit thymocyte differentiation, as indicated by unaltered thymocyte expression of CD4, CD8, and heat-stable antigens. These data may indicate that production of thymic atrophy and impairment of thymocyte differentiation by PAH involve separate mechanisms of action. Results of the present study additionally identify changes in immune cell populations that correlate well with inhibition of cell- and humoral-mediated immunity in experimental animals treated with DMBA.
Holladay
S D
SD
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University 24061-0442, USA.
Smith
B J
BJ
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D005260:Female; D005333:Fetus / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D005434:Flow Cytometry; D005865:Gestational Age; D006410:Hematopoiesis / Q000187:drug effects*; D007108:Immune Tolerance / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D018811:Maternal Exposure; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D013723:Teratogens / Q000633:toxicity*; D013950:Thymus Gland / Q000187:drug effects* / Q000196:embryology / Q000276:immunology / Q000473:pathology
D015704:CD4 Antigens; D016827:CD8 Antigens; D013723:Teratogens; D015127:9,10-Dimethyl-1,2-benzanthracene