POSSIBLE OF ROLE OF AVIAN RETROVIRUSES IN HUMAN CANCER

我们进行的初步研究表明，高度暴露于禽白血病/肉瘤病毒(ALSV)或有可能接触这种病毒的家禽工作者以及死于癌症的人的肿瘤细胞基因组可能携带整合的ALSV。这一观察是基于从五个石蜡肿瘤块中提取的DNA的检测，这些患者使用聚合酶链式反应(PCR)进行了检测。使用相同的引物，从45名相似暴露的健康家禽工作者和45名健康人群对照的外周血淋巴细胞中提取的DNA的PCR扩增没有检测到任何整合的ALSV。由于资源有限，不可能将这些测试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，他们将提供ALSV参与人类癌症发生的第一个证据。人类通常接触禽白血病/肉瘤病毒(ALSV)，这种病毒会自然感染鸡并导致癌症。ALSV在体外可以感染和转化人类细胞；在实验上，灵长类动物可以在体内感染并诱发肿瘤。最近对世界各地肉类行业工人的流行病学研究，包括接触这些病毒最多的受试者，一直报告这一群体中超过某些癌症。我们和其他人首次提供了血清学证据，证明人类暴露在这些病毒中，在暴露的人类受试者的血清中存在针对ALSV的特异性抗体。现在证明ALSV在人类癌症病因学中有罪所需的唯一证据是一致地证明整合在癌症患者肿瘤细胞基因组中的病毒的存在。在这项应用中，我们建议通过测试尽可能多的ALSV暴露工人死于癌症的人类DNA样本以及各种合适的对照样本来确认我们的初步发现。在暴露的肿瘤样本的基因组中证实了ALSV前病毒DNA，而在对照肿瘤样本中没有，这将为ALSV在人类致癌中的作用提供确凿的证据。

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.