IMMUNOSUPPRESSION FOLLOWING 7,12-DIMETHYLBENZ[A]ANTHRACENE EXPOSURE IN B6C3F1 MICE .2. ALTERED CELL-MEDIATED-IMMUNITY AND TUMOR RESISTANCE
IMMUNOSUPPRESSION FOLLOWING 7,12-DIMETHYLBENZ[A]ANTHRACENE EXPOSURE IN B6C3F1 MICE .2. ALTERED CELL-MEDIATED-IMMUNITY AND TUMOR RESISTANCE
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DOI：
10.1016/0192-0561(86)90058-5
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发表时间：
1986-01-01
期刊：
影响因子：
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通讯作者：
ADAMS, DO
中科院分区：
文献类型：
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作者：
DEAN, JH;WARD, EC;ADAMS, DO
我们先前已经证明，多环芳烃苯并[a]芘(B[a]P)和7，12-二甲基苯并[a]蒽(DMBA)可以显著降低脾重量、脾和骨髓细胞数以及T依赖抗原所产生的IgM空斑形成细胞的数量。暴露于DMBA而不是B[a]P可增加对PYB6肿瘤细胞和单核细胞增生性李斯特菌攻击的敏感性，提示DMBA产生的免疫损伤涉及细胞免疫(CMI)和肿瘤耐药机制。在这项研究中，雌性B6C3F1小鼠在两周的时间里接受了10次皮下注射0.5、5或10微克/克体重的总剂量的5、50和100微克DMBA，并在最后一次注射DMBA后3-5天检测了CMI和肿瘤杀伤功能。DMBA染毒组小鼠脾细胞数减少62%，滞留腹膜细胞数减少47%，但T细胞和T细胞亚群、B细胞和巨噬细胞在染毒小鼠脾中的比例没有改变。PHA、ConA和LPS对有丝分裂原诱导的淋巴细胞转化的抑制率分别为49%、48%和76%。在单向混合淋巴细胞培养中，DMBA对同种异体抗原的反应被抑制了73%。细胞毒性T细胞(CTL)介导的肿瘤细胞溶解在50和100微克DMBA/g体重(分别被抑制88-95%)和自然杀伤细胞(NK)介导的肿瘤细胞溶解(分别被抑制24%和55%)中受到损害。在最高剂量暴露组，抗体依赖的细胞毒作用显著降低。DMBA处理的小鼠腹膜巨噬细胞聚集减少，但存在的巨噬细胞被推向激活。DMBA暴露的小鼠从肺部静脉注射B16F10肿瘤细胞的能力没有受到损害。由于NK和分枝杆菌介导的肿瘤细胞毒性被认为是B16F10黑色素瘤细胞被肺部清除的主要原因，因此在DMBA暴露后观察到的NK抑制程度似乎不足以改变体内B16F10的肺清除。相反，CTL杀瘤反应的丧失与PYB6肿瘤细胞攻击后肿瘤发生率的增加有关。
We have previously demonstrated that the polycyclic aromatic hydrocarbons benzo[a]pyrene (B[a]P) and 7,12-dimethylbenz[a]anthracene (DMBA) produce a marked decrease in spleen weight, spleen and bone marrow cellularity and the number of IgM plaque forming cells generated in response to a T-dependent antigen. Exposure to DMBA, but not B[a]P, increased susceptibility to challenge with PYB6 tumor cells and Listeria monocytogenes suggesting that DMBA produces immune impairment involving cell-mediated immunity (CMI) and tumor resistance mechanism. In this study, female B6C3F1 mice received total doses of 5, 50 and 100 .mu.g DMBA/g of body weight in ten subcutaneous injections of 0.5, 5, or 10 .mu.g/g over a 2 week period and CMI and tumoricidal functions were examined 3-5 days following the final injection of DMBA. DMBA exposed mice exhibited suppressed splenic cellularity (decreased 62%) and decreased numbers of resident peritoneal cells (down to 47% of control), although the proportion of T cell and T cell subsets, B cells and macrophages in spleens from exposed mice was not altered. Lymphocyte blastogenesis in response to mitogens was suppressed up to 49% with PHA, 48% with Con A and 76% with LPS. The response to alloantigens in unidirectional mixed lymphocyte culture was depressed as much as 73% following exposure to DMBA. Tumor cytolysis mediated by cytotoxic T cells (CTL) was impaired at doses of 50 and 100 .mu.g DMBA/g body weight (88-95% suppressed respectively) as was natural killer cell (NK)-mediated tumor cytolysis(24% and 55% suppressed). Antibody-dependent cytotoxicity was significantly depressed in the highest exposure group. Peritoneal macrophage accumulation was decreased in DMBA-treated mice, but the macrophages present were pushed towards activation. The ability of DMBA-exposed mice to eliminate intravenously injected B16F10 tumor cells from the lungs was not impaired. Since NK- and M.phi.-mediated tumor cytotoxicity are thought to be primarily responsible for pulmonary elimination of B16F10 melanoma cells, the extent of NK suppression observed following DMBA exposure appeared to be insufficent to alter in vivo B16F10 pulmonary elimination. In contrast, the loss of the CTL tumoricidal response correlated with an increased frequency of tumors following challenge with PYB6 tumor cells.