Distribution and characterization of environmental promoter substances as assayed by synergistic Epstein-Barr virus-activating system.

The application of a new screening procedure which utilizes the synergistic effect of short-chain fatty acids and tumor-promoting diterpene esters enabled rapid and easy detection of environmental substances with Epstein-Barr virus (EBV)-activating/tumor-promoting potency. Over 500 samples were tested and more than 30 substances with such activities were identified. Most, if not all, were plant diterpene esters derived from Euphorbiaceae and Thymelaeaceae families and a few were indole alkaloids of microbial origin. We attempted to link these laboratory findings with those of epidemiological field studies on three virus-associated diseases, Burkitt's lymphoma, nasopharyngeal carcinoma, and adult T-cell leukemia/lymphoma, which are known to have a peculiar geographical distribution. Our hypothesis was that EBV-activating/tumor-promoting substances might be present in the abundant areas where such diseases are endemic. We noticed that many active diterpene ester-containing plants are widely used as herbal medicaments in Africa and China and determined many plant species that had such activities. One example is Aleurites fordii, a plant commonly grown in Southern China for industrial purposes which yielded a potent promoter substance (12-O-hexadecanoyl-16-hydroxyphorbol-13-acetate, HHPA). The active diterpene esters were purified and their possible mechanism was studied from the view of receptor-binding, protein kinase C activation and transmembrane signaling.