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Lipid Peroxidation, Chronic Oxidative Stress and Breast Cancer Inci-dence: Implications for Breast Cancer Prevention

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Final rept. 1 Jul 2005-30 Jun 2007

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The experiments were based on the following interrelated hypotheses a Exposure of the mammary epithelium ME to chronic oxidative stress OxS underlies the high breast cancer BC incidence associated with Western industrialized environmentlifestyle and b that there is a positive correlation between BC incidence within a population and the prevalence within that population of protein adducts of the well-documented marker of chronic OxS 4-hydroxy-2-nonenal 4HNE that is a major breakdown product of lipid peroxidation caused by OxS. The PI had available for this research a archived forensic breast tissue from women without BC from two populations in SW USA with an over three-fold difference in BC incidence and b reduction mammoplasty specimens from women representative of the high BC incidence population served by her institution. A qualitative survey of tissue sections from 247 women from the three populations confirmed the pilot observation of a higher prevalence of 4HNE immunostaining of mammary epithelial ME in high BC risk populations and that 4HNE adducts are present in the ME already in many teenagers in that populations. However the marked heterogeneity in extent localization and intensity of the 4HNE immunostaining proved an obstacle to achieving the research goals by the proposed conventional semiquantitative scoring method for assessing immunostaining. Hence in order to obtain a more objective and quantitative measure of immunostaining effort was directed towards adapting to the task recently developed cytometric methods specifically a the application of densitometric image analysis to mammary ductal units extracted from digitized images of immunostained tissue sections and b multiplex immunoblotting of proteins transferred from tissue sections a method that allows for assessing levels of multiple epitopes normalized to total protein.

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  • Anatomy and Physiology
  • Medicine and Medical Research

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