Holladay S D, Smith B J
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University 24061-0442, USA.
Environ Res. 1995 Feb;68(2):106-13. doi: 10.1006/enrs.1995.1014.
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.
将ICR小鼠在妊娠期暴露于环境污染物7,12-二甲基苯并[a]蒽（DMBA），用于（i）研究这种化学物质的发育免疫毒性，以及（ii）在一个敏感的发育模型中评估可能参与这种致癌多环芳烃（PAH）诱导的免疫抑制的潜在造血细胞靶点。DMBA在胎鼠胸腺和肝脏中均产生了剂量依赖性的细胞减少。通过CD44、CD45R和Mac-1单克隆抗体结合鉴定的胎肝中常驻造血细胞亚群，在妊娠期接受DMBA处理后减少。特别是，胎肝中CD45R + B系淋巴细胞的总数因DMBA而减少至对照水平的20%。与先前有关相关PAH的报道不同，DMBA并未抑制胸腺细胞分化，CD4、CD8和热稳定抗原的胸腺细胞表达未发生改变即表明了这一点。这些数据可能表明PAH导致胸腺萎缩和胸腺细胞分化受损涉及不同的作用机制。本研究结果还确定了免疫细胞群体的变化，这些变化与用DMBA处理的实验动物中细胞介导和体液介导免疫的抑制密切相关。
