PROMOTION BY POLYCHLORINATED-BIPHENYLS OF LUNG AND LIVER-TUMORS IN MICE
PROMOTION BY POLYCHLORINATED-BIPHENYLS OF LUNG AND LIVER-TUMORS IN MICE
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DOI：
10.1093/carcin/15.10.2245
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发表时间：
1994-10-01
期刊：
影响因子：
4.7
通讯作者：
RIGGS, CM
中科院分区：
文献类型：
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作者：
ANDERSON, LM;LOGSDON, D;RIGGS, CM
多氯联苯（PCB）是肿瘤促进剂，几十年来一直在人体组织中发现。由于人类癌症潜伏期长和肿瘤促进的性质，它们对癌症风险的贡献可能现在才开始显现。在多氯联苯接触或组织含量与几个地点的癌症之间发现了流行病学联系。在啮齿类动物中，除了肝脏以外，几乎没有对多氯联苯促进肿瘤的研究。此前，在一项模拟婴儿致癌物暴露的实验中，在牛奶中接受多氯联苯后，肺和肝脏肿瘤，由环境亚硝胺N-亚硝基二甲胺（NDMA）在小鼠体内引发，随后用Aroclor 1254治疗。本研究旨在确认和表征Aroclor 1254对肿瘤数量、潜伏期、大小和恶性程度的影响。雄性Swiss小鼠在出生后第4天给予NDMA，在第8天给予Aroclor 1254（250 mg/kg），并间隔处死。对尸体中的八种多氯联苯同系物进行了定量。在28周龄时，NDMA引发的肺部肿瘤的小鼠的发病率因PCB而增加了2.5倍。多氯联苯在28周和52周时使肺肿瘤的多样性增强了4倍。到72周，仅NDMA组和NDMA-PCB组的肿瘤数量相似。肝脏肿瘤在52周时首次出现，并且仅在接受NDMA和PCB的小鼠中出现。至于肺，在72周时，仅NDMA组和NDMA -PCB组的发病率都很高。PCB治疗对肿瘤大小和肝癌发病率无明显影响。尸体分析显示，28周时肺肿瘤数量与2，2 '，4，4'，5-五氯联苯的相对百分比之间存在显著正相关，没有其他相关性。结果证实，多氯联苯促进肺部以及肝脏肿瘤，通过触发潜伏启动肿瘤的早期出现，否则在老年出现。
Polychlorinated biphenyls (PCB), which are tumor promoters, have been found in human tissues for decades. Their contribution to cancer risk may only now start to appear, due to long human cancer latency and the nature of tumor promotion. Epidemiological associations have been seen between PCB exposure or tissue content and cancer at several sites. In rodents, tumor promotion by PCBs has been little studied in tissues other than liver. Previously, in an experiment modeling infant carcinogen exposure following PCBs received in milk, lung and liver tumors, initiated neonatally in mice by the environmental nitrosamine N-nitrosodimethylamine (NDMA), were promoted by later treatment with Aroclor 1254. The present study was undertaken to confirm and characterize the effects of Aroclor 1254 on tumor number, latency, size and malignancy. Male Swiss mice were given NDMA on postnatal day 4 and Aroclor 1254 (250 mg/kg) on day 8, and killed at intervals. Eight PCB congeners were quantified in the carcasses. Incidences of mice with NDMA-initiated lung tumors at 28 weeks of age were increased 2.5-fold by PCBs. Multiplicities of lung tumors were enhanced four-fold by PCBs at 28 and 52 weeks. By 72 weeks tumor numbers were similar in the NDMA-only and NDMA-PCB groups. Liver tumors first occurred in significant numbers at 52 weeks and only in mice receiving both NDMA and PCBs. As for the lung, at 72 weeks the incidence was high in both the NDMA-only and NDMA -PCB groups. Sizes of tumors and liver carcinoma incidence were not altered by PCB treatment. Carcass analysis revealed a significant positive association between lung tumor numbers at 28 weeks and relative percentage of 2,2',4,4',5-pentachlorobiphenyl, with no other correlations. The results confirm that PCBs promote lung as well as liver tumors, by triggering the early appearance of latent initiated tumors otherwise presenting in old age.