Anderson L M, Logsdon D, Ruskie S, Fox S D, Issaq H J, Kovatch R M, Riggs C M
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Ft Detrick, MD 21702-1201.
Carcinogenesis. 1994 Oct;15(10):2245-8. doi: 10.1093/carcin/15.10.2245.
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.
多氯联苯（PCB）是肿瘤促进剂，几十年来一直在人体组织中被发现。由于人类癌症潜伏期长以及肿瘤促进的性质，它们对癌症风险的影响可能现在才开始显现。在多氯联苯暴露或组织含量与多个部位的癌症之间已观察到流行病学关联。在啮齿动物中，除肝脏外，多氯联苯在其他组织中的肿瘤促进作用研究较少。此前，在一项模拟婴儿通过牛奶摄入多氯联苯后致癌物暴露的实验中，环境亚硝胺N-亚硝基二甲胺（NDMA）在新生小鼠中引发的肺和肝肿瘤，在后期用Aroclor 1254处理后得到促进。本研究旨在确认并表征Aroclor 1254对肿瘤数量、潜伏期、大小和恶性程度的影响。雄性瑞士小鼠在出生后第4天给予NDMA，在第8天给予Aroclor 1254（250毫克/千克），并定期处死。对尸体中的8种多氯联苯同系物进行了定量分析。在28周龄时，多氯联苯使由NDMA引发的肺肿瘤小鼠的发病率增加了2.5倍。在28周和52周时，多氯联苯使肺肿瘤的数量增加了四倍。到72周时，仅接受NDMA和接受NDMA与多氯联苯的两组小鼠的肿瘤数量相似。肝肿瘤在52周时首次大量出现，且仅出现在同时接受NDMA和多氯联苯的小鼠中。与肺一样，在72周时，仅接受NDMA和接受NDMA与多氯联苯的两组小鼠的发病率都很高。多氯联苯处理未改变肿瘤大小和肝癌发病率。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，无其他相关性。结果证实，多氯联苯通过触发原本在老年才会出现的潜伏性起始肿瘤的早期出现，促进了肺和肝肿瘤的发生。
