Products of γ-tocopherol reaction with NO2 and their formation in rat insulinoma (RINm5F) cells

γ-Tocopherol, commonly found in seed oils, is the major tocopherol in the U.S. diet, is superior to α-tocopherol in preventing neoplastic transformation, and demonstrates unique reactivity toward NO2. This article describes the products of reaction between γ-tocopherol and low concentrations of gaseous nitrogen dioxide (NO2), as well as their endogenous formation in NO-producing RINm5F cells. γ-Tocopherol in hexane reacts with NO2 to yield two products identified as 2,7,8-trimethyl-2(4,8,12-trimethyltridecyl)-5,6-chromaquinone, “tocored,” and 2,7,8 trimethyl-2(4,8,12-trimethyldecyl) 5-nitro, 6-chromanol, “tocoyellow.” Physical data for these two compounds and reaction characteristics are described. The formation of tocored is consistent with a proposed mechanism of γ-tocopherol-mediated reduction of NO2 to NO involving initial reaction by NO2 at the C-5 position to form an intermediate nitrite ester tocopheryl radical, which then reacts internally to release NO and form 5,6 epoxy γ-tocopherol. Tautomerization and further oxidation of the latter intermediate by NO2 yields tocored as the main product observed. The reaction of γ-tocopherol with NO2 to form NO occurs independently of light, whereas a-tocopherol requires light to generate NO from NO2. γ-Tocopherol and aminoguanidine, an NO synthase inhibitor, were superior to α-tocopherol in preventing RINm5F cell toxicity induced by Interleukin-1β (IL-1β). Both tocored and tocoyellow were observed to form in RINm5F cells loaded with γ-tocopherol and producing NO constitutively, although a consistent increase in these products as a result of induced NO synthesis was not observed.