Abstract
Substantial evidence has implicated Epstein–Barr virus (EBV) in the aetiology of two human neoplasms, nasopharyngeal carcinoma (NPC) and Burkitt's lymphoma1,2. This is supported by the presence of high antibody titres to EBV early antigen and virus capsid antigen3,4, as well as antibody to two viral-associated enzymes, DNase and DNA polymerase5,6. Patients with NPC, particularly the undifferentiated form, are commonly found to have EBV DNA in the tumour2. Ito and others7–10 have presented strong epidemio-logical evidence that phorbol esters are related to the unusual geographic distribution of NPC in southeastern regions of China. There appears to be a close link between the widespread EBV infection of the Asian population and the distinct regional distribution in China of plants that produce diterpene ester11. Naturally occurring phorbol esters are produced by plants of the Euphor-biaceae and Thymelaeaceae, which are used as traditional herbal medicines12. Although it has been established that EBV can infect epithelial cells isolated from NPC as well as certain normal epithelial cells13–15, there has been no in vitro evidence that EBV induces neoplastic transformation in normal human epithelial cells with or without exposure to phorbol esters. We report here evidence that transformation of normal human epithelial cells results from exposure to infectious EBV and that transformation is dependent on the presence of phorbol esters.
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Tomei, L., Noyes, I., Blocker, D. et al. Phorbol ester and Epstein—Barr virus dependent transformation of normal primary human skin epithelial cells. Nature 329, 73–75 (1987). https://doi.org/10.1038/329073a0
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DOI: https://doi.org/10.1038/329073a0
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