POSSIBLE OF ROLE OF AVIAN RETROVIRUSES IN HUMAN CANCER

我们开展的初步研究表明，高度暴露于禽类白血病/肉瘤病毒（ALSV）或有可能暴露于这种病毒并死于癌症的家禽工人的肿瘤细胞基因组可能携带整合的ALSV。这一观察结果是基于我们使用聚合酶链反应（PCR）试验对从这些患者的五个石蜡肿瘤块中提取的DNA进行检测。使用相同的引物，从45名同样暴露的健康家禽工人和45名健康人群对照的外周血淋巴细胞中提取的DNA进行PCR扩增，未检测到任何整合的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参与人类癌变的第一个证据。人类通常会接触禽白血病/肉瘤病毒（ALSV），这种病毒会自然感染鸡并导致鸡患上癌症。ALSV能在体外感染和转化人细胞；在实验中，灵长类动物可以在体内被感染并诱发肿瘤。最近对全世界肉类工业工人（包括接触这些病毒最多的对象）进行的流行病学研究一致报告说，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，通过证明在暴露的人类受试者的血清中存在专门针对ALSV的抗体。现在唯一需要证明ALSV与人类癌症病因有关的证据是，持续地证明该病毒存在于癌症患者肿瘤细胞的基因组中。在这项应用中，我们建议通过在尽可能多的死于癌症的暴露于ALSV的工人的DNA样本中检测ALSV病毒整合来证实我们的初步发现，以及测试各种合适的对照样本。在暴露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却没有，这将为ALSV在人类致癌作用中提供明确的证据。

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.