POSSIBLE OF ROLE OF AVIAN RETROVIRUSES IN HUMAN CANCER

我们已经进行的初步研究表明，来自高度暴露于禽白血病/肉瘤病毒（ALSV）的家禽工人的肿瘤细胞的基因组，或具有这种暴露的可能性，并且死于癌症的人可能携带整合的ALSV。这一观察结果是基于我们使用聚合酶链反应（PCR）检测从这些患者的五个石蜡肿瘤块中提取的DNA的检查。使用相同的引物，PCR扩增的DNA提取的外周血淋巴细胞从45个类似的接触健康家禽工人和45个健康人群对照没有检测到任何集成ALSV。由于资源有限，不可能将这些试验扩展到控制未暴露的人类肿瘤样本。如果这些初步发现能够得到证实，它们将提供ALSV参与人类致癌作用的第一个证据。人类通常暴露于禽白血病/肉瘤病毒（ALSV），这些病毒自然感染鸡并导致鸡患癌症。ALSV可以在体外感染并转化人类细胞;实验上，灵长类动物可以在体内感染并诱导肿瘤。最近对全世界肉类工业工人的流行病学研究，包括接触这些病毒最多的受试者，一致报告这一群体中某些癌症的发病率过高。我们和其他人首次提供了血清学证据，证明人类暴露于这些病毒，证明暴露的人类受试者血清中存在特异性抗ALSV的抗体。现在证明ALSV在人类癌症病因学中的唯一证据是一致地证明整合在癌症受试者的肿瘤细胞基因组内的病毒的存在。在本申请中，我们建议通过在尽可能多的死于癌症的ALSV暴露工人的人类DNA样本中检测ALSV病毒整合，以及检测各种合适的对照样本，来证实我们的初步发现。经证实，ALSV前病毒DNA存在于暴露的肿瘤样本的基因组中，但不存在于对照肿瘤样本的基因组中，这将为ALSV参与人类致癌作用提供明确的证据。

Preliminary studies we have carried out indicate that the genome of tumor cells from poultry workers highly exposed to avian leukosis/sarcoma viruses (ALSV), or with potential for such an exposure, and who died of cancer may carry integrated ALSV. This observation was based on the examination of DNA extracted from five paraffin tumor blocks from such patients we had tested using the polymerase chain reaction (PCR) assay. Using the same primers, PCR amplification of DNA extracted from peripheral blood lymphocytes from 45 similarly exposed healthy poultry workers and 45 healthy population controls did not detect any integrated ALSV. Due to limited resources, it was not possible to extend these tests to control unexposed human tumor samples. If these initial findings can be confirmed, they will provide the first evidence that ALSV are involved in human carcinogenesis. Humans are commonly exposed to avian leukosis/sarcoma viruses (ALSV) which naturally infect and cause cancer in chickens. ALSV can infect and transform human cells in vitro; and experimentally, primates can be infected and tumors induced in them in vivo. Recent epidemiological studies of workers in the meat industry worldwide who include subjects with the highest exposure to these viruses consistently report excess of certain cancers in this group. We and others have provided serological evidence for the first time ever, that humans are exposed to these viruses, by the demonstration of the presence of antibodies specifically directed against ALSV in the sera of exposed human subjects. The only piece of evidence now needed to incriminate ALSV in the etiology of human cancers is to consistently demonstrate the presence of the virus integrated within the genome of tumor cells of subjects with cancer. In this application, we propose to confirm our initial findings by testing for ALSV viral integration in as many more human DNA samples from ALSV-exposed workers who died of cancer, as possible, as well as testing a variety of suitable control samples. The confirmed demonstration of ALSV pro-viral DNA in the genome of exposed tumor samples but not in that of control tumor samples, will provide definitive evidence incriminating ALSV in human carcinogenesis.