Dynamics of oxidative damage at early stages of estrogen-dependant carcinogenesis

Abstract

The objective of this study was to assess the dynamics of oxidative damage to cellular macromolecules such as proteins, lipids, and DNA under conditions of oxidative stress triggering early stages of estrogen-dependent carcinogenesis. A rodent model of carcinogenesis was used. Syrian hamsters were sacrificed after 1, 3, 5h and 1 month from the initial implantation of 17β-estradiol (E2). Matching control groups were used. Kidneys as target organs for E2-mediated oxidative stress were excised and homogenized for biochemical assays. Subcellular fractions were isolated. Carbonyl groups (as a marker of protein oxidation) and lipid hydroxyperoxides were assessed. DNA was isolated and 8-oxodGuo was assessed. Electron paramagnetic resonance spectroscopy was used to confirm the results for lipid peroxidation. Exposition to E2 in rodent model leads to a damage of macromolecules of the cell, including proteins and DNA, but not lipids. Proteins appear to be primary target of the damage but are shortly followed by DNA. It has previously been speculated that protein peroxides can increase DNA modifications. This time sequence was observed in our study. Nevertheless, direct relation between protein and DNA damage still remains unsolved. © 2008 Springer Science+Business Media, LLC.