E1A-3Y1 CELL-SPECIFIC TOXICITY OF TEA POLYPHENOLS AND THEIR KILLING MECHANISM

To screen carcinostatic components in foodstuffs, the toxicity of tea polyphenols was compared between rat 3Y1 diploid fibroblasts and a var iety of their virally transformed cells. Among tea polyphenols tested, epigallocatechin gallate killed 3Y1 cells transformed by E1A gene of human adenovirus type 12 (E1A-3Y1 cells) at a 100 times lower concentr ation than the parental 3Y1 cells. Epigallocatechin gallate also exert ed a strong E1A-3Y1 cell-specific toxicity, while epicatechin and epic atechin gallate did not. When the activity of three antioxidant enzyme s was compared between 3Y1 and its transformants, catalase activity wa s markedly low in the latter, especially in E1A-3Y1 cells, and the sub strate of the enzyme, hydrogen peroxide, exerted a toxicity specific t o this cell line. Then the inhibitory activities of various chemicals on E1A-3Y1 cell-specific toxicity of phospholipids or catechol were ex amined. Among lipoxygenase inhibitors, all of the polyphenolic compoun ds inhibited the toxicity of phospholipids, but not a nonpolyphenolic inhibitor (clofibrate). Two phospholipase A,inhibitors (dexamethasone and quinacrine) did not inhibit the toxicity. These results indicate t hat the triphenol structure of the B ring is essential for the E1A-3Y1 cell-specific toxicity of tea polyphenols, and that the decrease in c atalase activity is partially responsible for the higher sensitivity o f E1A-3Y1 cells against the polyphenols. The inhibitory effect of poly phenolic lipoxygenase inhibitors is ascribed at least in part to their antioxidant activities.