title: Modulatory effects of alpha- and gamma-tocopherols on 4-hydroxyestradiol induced oxidative stresses in MCF-10A breast epithelial cells.
abstract: The elevated level of circulating estradiol increases the risk of breast tumor development. To gain further insight into mechanisms involved in their actions, we investigated the molecular mechanisms of 4-hydroxyestradiol (4-OHE(2)) to initiate and/or promote abnormal cell growth, and of alpha- or gamma-tocopherol to inhibit this process. MCF-10A, human breast epithelial cells were incubated with 0.1 microM 4-OHE(2), either with or without 30 microM tocopherols for 96 h. 4-OHE(2) caused the accumulation of intracellular ROS, while cellular GSH/GSSG ratio and MnSOD protein levels were decreased, indicating that there was an oxidative burden. 4-OHE(2) treatment also changed the levels of DNA repair proteins, BRCA1 and PARP-1. gamma-Tocopherol suppressed the 4-OHE(2)-induced increases in ROS, GSH/GSSG ratio, and MnSOD protein expression, while alpha-tocopherol up-regulated BRCA1 and PARP-1 protein expression. In conclusion, 4-OHE(2) increases oxidative stress reducing the level of proteins related to DNA repair. Tocopherols suppressed oxidative stress by scavenging ROS or up-regulating DNA repair elements.
authors.affiliation: Department of Food and Nutrition, Sookmyung Women's University, 52 Hyochangwon-gil, Yongsan-gu, Seoul 140-742, Korea.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Lee
authors.forename: Seung-Yeon
authors.initials: SY
authors.lastname: Oh
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Sei Hyun
authors.initials: SH
authors.lastname: Ahn
authors.forename: Byung Ho
authors.initials: BH
authors.lastname: Son
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Sung