Immunosuppression following 7,12-dimethylbenz[a]anthracene exposure in B6C3F1 mice. I. Effects on humoral immunity and host resistance.
Immunosuppression following 7,12-dimethylbenz[a]anthracene exposure in B6C3F1 mice. I. Effects on humoral immunity and host resistance.
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B6C3F1 小鼠暴露于 7,12-二甲基苯并[a]蒽后的免疫抑制。
DOI：
10.1016/0041-008x(84)90212-6
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发表时间：
1984
影响因子：
3.8
通讯作者：
J. Dean
中科院分区：
文献类型：
--
作者：
E. C. Ward;M. Murray;L. Lauer;R. House;R. Irons;J. Dean
先前已经证明，多环芳烃（PAH），苯并(a)芘（B[a]P）抑制B细胞分化的最终步骤，导致t依赖性和B-2 t非依赖性抗原的抗体产生减少。本研究的目的是确定这种效应是对致癌性多环芳烃的普遍影响还是对苯并[a]芘的特异性影响。B6C3F1雌性小鼠分别以0.5、5或10 μg/g的剂量（即总剂量为5、50和100 μg/g） 10次皮下注射多环芳烃7,12-二甲基苯[a]蒽（DMBA）。最后一次注射后3 ~ 5天进行免疫功能和宿主耐药性测定。10 μg/g剂量可使大鼠脾脏重量、脾脏和骨髓细胞数量明显减少，胸腺和体重无明显变化。脾前体细胞体外生成b淋巴细胞集落的能力在10 μg/g剂量下也受到抑制。暴露于5 μg/g或更高浓度的DMBA导致IgM斑块形成细胞数量减少高达97%，这是对t依赖性抗原羊红细胞（SRBC）的反应。IgG对SRBC的反应同样下降。10 μg/g时，IgM对半抗原偶联t -非依赖性抗原三硝基苯脂多糖（TNP- lps） （B-1细胞特异性）和三硝基苯(TNP)-Ficoll （B-2细胞特异性）的反应也被抑制（分别为88%和97%）。与B[a]P暴露相比，DMBA暴露导致小鼠对PYB6可移植肉瘤和单核细胞增生李斯特菌的易感性增加，而B[a]P暴露对宿主耐药试验没有影响。因此，DMBA，一种比B[a]P更强的致癌物，比B[a]P产生更广泛的B细胞抑制，并改变宿主对肿瘤和细菌攻击的抵抗力。
It has previously been demonstrated that the polycyclic aromatic hydrocarbon (PAH), benzo(a)pyrene (B[a]P), suppresses the terminal step in B-cell differentiation, resulting in a decrease in antibody production to T-dependent and B-2 T-independent antigens. The purpose of this study was to ascertain if this effect was common to carcinogenic PAHs or specific for B[a]P. The PAH 7,12-dimethylbenz[a]anthracene (DMBA) was administered to B6C3F1 female mice by ten sc injections of 0.5, 5, or 10 μg/g over a 2-week period (i.e., total dose of 5, 50, and 100 μg/g). Immune function and host resistance assays were performed 3 to 5 days following the last injection. The 10 μg/g dosage resulted in a marked decrease in spleen weights and spleen and bone marrow cellularity, while thymus and body weights were not significantly altered. The ability to generate B-lymphocyte colonies in vitro from spleen precursor cells was also suppressed at the 10 μg/g dose. Exposure to DMBA at 5 μg/g or greater resulted in a reduction of up to 97% in the number of IgM plaque-forming cells in response to the T-dependent antigen sheep red blood cells (SRBC). The IgG response to SRBC was similarly depressed. The IgM response to the hapten-conjugated T-independent antigens trinitrophenyl-lipopolysaccharide (TNP-LPS) (specific for B-1 cells) and trinitrophenyl (TNP)-Ficoll (Specific for B-2 cells) was also depressed (88 and 97%, respectively) at 10 μg/g. DMBA exposure resulted in an increased susceptibility to challenge with the PYB6 transplantable sarcoma and the bacterium Listeria monocytogenes, in contrast to B[a]P exposure, which had no effect on host resistance assays. Thus, DMBA, a more potent carcinogen than B[a]P, produces a more extensive B-cell suppression than B[a]P as well as alters host resistance to tumor and bacterial challenge.