|1R03CA083096-01A1 Interpret this number
|Tulane University Of Louisiana
|Possible of Role of Avian Retroviruses in Human Cancer
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.