期刊
CANCER DETECTION AND PREVENTION
卷 29, 期 4, 页码 383-388出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.cdp.2005.03.003
关键词
alpha-tocopherol; alpha-tocotrienol; 17 beta-estradiol epoxide; chemoprevention; breast cancer; nuclear RNA synthesis; dimethyldioxirane (DMDO); rat liver nuclei; liver microsomes; vitamin E; cancer prevention; unsaturated fatty acid; nuclear RNA synthesis; dimethyldioxirane (DMDO); rat liver nuclei; liver microsomes; vitamin E; cancer prevention; unsaturated fatty acids
类别
Background: We found that 17 beta-estradiol (E-2) could be activated by epoxidation to bind DNA and to inhibit nuclear RNA synthesis. Vitamin E compounds are powerful antioxidants and chain-breaking free radical scavengers. The chromanol ring in Vitamin E is believed to be involved in these reactions. Methods: Here, we examined the preventive effect of a-tocopherol, alpha-, gamma- and delta-tocotrienols on E-2 activation. Results: We found that when any one of these Vitamin E compounds was mixed with E-2 for epoxidation by the epoxide-forming oxidant dimethyldioxirane (DMDO), a-tocopherol was the least effective as compared with the tocotrienols against the formation of E-2 epoxide as reflected by the loss of the ability of E-2 to inhibit nuclear RNA synthesis. This conclusion was further confirmed by the binding studies of [H-3] labeled E-2 to DNA using either DMDO or liver microsomes activation system. Conclusions: Since the chromanol ring is shared by both tocopherols and tocotrienols and the only difference between these two subgroups of Vitamin E is the phytol side chain, we conclude that the polyunsaturated phytol group in tocotrienols plays a key preventive role in E-2 epoxidation. This is the first report showing that the polyunsaturated phytol side chain in tocotrienols is involved in an antioxidative activity and it may also have a preventive effect against the E-2 epoxide induced breast cancer carcinogenesis at the initiation. (c) 2005 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved.
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