Products of gamma-tocopherol reaction with NO2 and their formation in rat insulinoma (RINm5F) cells.
gamma-Tocopherol, commonly found in seed oils, is the major tocopherol in the U.S. diet, is superior to alpha-tocopherol in preventing neoplastic transformation, and demonstrates unique reactivity toward NO2. This article describes the products of reaction between gamma-tocopherol and low concentrations of gaseous nitrogen dioxide (NO2), as well as their endogenous formation in NO-producing RINm5F cells. gamma-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-trimethyltridecyl) 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 gamma-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 gamma-tocopherol. Tautomerization and further oxidation of the latter intermediate by NO2 yields tocored as the main product observed. The reaction of gamma-tocopherol with NO2 to form NO occurs independently of light, whereas alpha-tocopherol requires light to generate NO from NO2. gamma-Tocopherol and aminoguanidine, an NO synthase inhibitor, were superior to alpha-tocopherol in preventing RINm5F cell toxicity induced by Interleukin-1 beta (IL-1 beta). Both tocored and tocoyellow were observed to form in RINm5F cells loaded with gamma-tocopherol and producing NO constitutively, although a consistent increase in these products as a result of induced NO synthesis was not observed.
Cooney
R V
RV
Cancer Research Center of Hawaii, Cancer Etiology Program, Honolulu 96813, USA.
Harwood
P J
PJ
Franke
A A
AA
Narala
K
K
Sundström
A K
AK
Berggren
P O
PO
Mordan
L J
LJ
D000818:Animals; D001711:Biotransformation; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D007340:Insulinoma / Q000378:metabolism*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism*; D010084:Oxidation-Reduction; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D051381:Rats; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000737:chemistry* / Q000378:metabolism*
D014810:Vitamin E; D009569:Nitric Oxide