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Title: δ- and γ-tocopherols inhibit phIP/DSS-induced colon carcinogenesis by protection against early cellular and DNA damages.

Authors: Chen, Jayson X; Liu, Anna; Lee, Mao-Jung; Wang, Hong; Yu, Siyuan; Chi, Eric; Reuhl, Kenneth; Suh, Nanjoo; Yang, Chung S

Published In Mol Carcinog, (2017 Jan)

Abstract: Tocopherols, the major forms of vitamin E, are a family of fat-soluble compounds that exist in alpha (α-T), beta (β-T), gamma (γ-T), and delta (δ-T) variants. A cancer preventive effect of vitamin E is suggested by epidemiological studies. However, past animal studies and human intervention trials with α-T, the most active vitamin E form, have yielded disappointing results. A possible explanation is that the cancer preventive activity of α-T is weak compared to other tocopherol forms. In the present study, we investigated the effects of δ-T, γ-T, and α-T (0.2% in diet) in a novel colon cancer model induced by the meat-derived dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by dextran sodium sulfate (DSS)-induced colitis in CYP1A-humanized (hCYP1A) mice. PhIP/DSS treatments induced multiple polypoid tumors, mainly tubular adenocarcinomas, in the middle to distal colon of the hCYP1A mice after 10 wk. Dietary supplementation with δ-T and γ-T significantly reduced colon tumor formation and suppressed markers of oxidative and nitrosative stress (i.e., 8-oxo-dG and nitrotyrosine) as well as pro-inflammatory mediators (i.e., NF-κB p65 and p-STAT3) in tumors and adjacent tissues. By administering δ-T at different time periods, we obtained results suggesting that the inhibitory effect of δ-T against colon carcinogenesis is mainly due to protection against early cellular and DNA damages caused by PhIP. α-T was found to be ineffective in inhibiting colon tumors and less effective in attenuating the molecular changes. Altogether, we demonstrated strong cancer preventive effects of δ-T and γ-T in a physiologically relevant model of human colon cancer. © 2016 Wiley Periodicals, Inc.

PubMed ID: 27175800 Exiting the NIEHS site

MeSH Terms: Animals; Anticarcinogenic Agents/therapeutic use*; Carcinogenesis/chemically induced; Carcinogenesis/drug effects*; Carcinogenesis/genetics; Carcinogenesis/metabolism; Colon/drug effects*; Colon/metabolism; Colonic Neoplasms/chemically induced; Colonic Neoplasms/genetics; Colonic Neoplasms/metabolism; Colonic Neoplasms/prevention & control*; Cytochrome P-450 CYP1A1/metabolism; DNA Damage/drug effects; Dextran Sulfate; Humans; Imidazoles; Male; Mice; Oxidative Stress/drug effects; Tocopherols/therapeutic use*; Vitamins/therapeutic use*; gamma-Tocopherol/therapeutic use*

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