title: δ- and γ-tocopherols, but not α-tocopherol, inhibit colon carcinogenesis in azoxymethane-treated F344 rats.
abstract: The cancer preventive activity of vitamin E has been extensively discussed, but the activities of specific forms of tocopherols have not received sufficient attention. Herein, we compared the activities of δ-tocopherol (δ-T), γ-T, and α-T in a colon carcinogenesis model. Male F344 rats, seven weeks old, were given two weekly subcutaneous injections of azoxymethane (AOM) each at a dose of 15 mg/kg body weight. Starting 1 week before the AOM injection, the animals were maintained on a modified AIN76A diet, or the same diet containing 0.2% of δ-T, γ-T, α-T, or a γ-T-rich mixture of tocopherols (γ-TmT), until the termination of the experiment at 8 weeks after the second AOM injection. δ-T treatment showed the strongest inhibitory effect, decreasing the numbers of aberrant crypt foci by 62%. γ-T and γ-TmT were also effective, but α-T was not. Immunohistochemical analysis showed that δ-T and γ-T treatments reduced the levels of 4-hydroxynonenal and nitrotyrosine and the expression of cyclin D1 in the colon, preserved the expression of PPAR-γ, and decreased the serum levels of prostaglandin E2 and 8-isoprostane. Supplementation with 0.2% δ-T, γ-T, or α-T increased the respective levels of tocopherols and their side-chain degradation metabolites in the serum and colon tissues. Rather high concentrations of δ-T and γ-T and their metabolites were found in colon tissues. Our study provides the first evidence for the much higher cancer preventive activity of δ-T and γ-T than α-T in a chemically induced colon carcinogenesis model. It further suggests that δ-T is more effective than γ-T.
authors.affiliation: Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Guan
authors.forename: Guangxun
authors.initials: G
authors.lastname: Li
authors.forename: Anna B
authors.initials: AB
authors.lastname: Liu
authors.forename: Mao-Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Yang
authors.forename: Yu-Kuo
authors.initials: YK
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.forename: Weichung
authors.initials: W
authors.lastname: Shih
authors.forename: Chung S
authors.initials: CS
authors.lastname: Yang
mesh_terms: D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001397:Azoxymethane / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000517:prevention & control*; D019938:Cyclin D1 / Q000096:biosynthesis; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008956:Models, Chemical; D051381:Rats; D011916:Rats, Inbred F344; D024505:Tocopherols / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000737:chemistry; D024502:alpha-Tocopherol / Q000378:metabolism*; D024504:gamma-Tocopherol / Q000378:metabolism*
chemical_list: D000447:Aldehydes; D016588:Anticarcinogenic Agents; D019938:Cyclin D1; C075750:8-epi-prostaglandin F2alpha; C002744:3-nitrotyrosine; D014443:Tyrosine; D024504:gamma-Tocopherol; D015237:Dinoprost; D024502:alpha-Tocopherol; C479072:delta-tocopherol; C027576:4-hydroxy-2-nonenal; D015232:Dinoprostone; D001397:Azoxymethane; D024505:Tocopherols