Hydrogen Peroxide-Induced Base Damage in Deoxyribonucleic Acid.

摘要

Hydrogen peroxide (H2O2) is ubiquitous in biological systems, formed as a consequence of a variety of metabolic processes. While normal cellular levels of H2O2 are generally low, these levels can be elevated as the result of inflammation, exposure to ionizing radiation, thiol oxidation, and metabolism of carcinogenic agents. As a low-molecular-weight and uncharged species, H2O2 can diffuse readily from the site of production and traverse cell membranes. In this investigation, methodology incorporating gas chromatography-mass spectrometry with selected ion monitoring (GC-MS/SIM) was used to reveal a wide spectrum of base products in DNA, which result from H2O2 exposure, and which are characteristic of those produced in DNA upon exposure to ionizing radiation. In addition, studies were performed to examine the mechanism of H2O2-induced damage to DNA, which has been suggested to involve a site-specific reaction catalyzed by trace quantities of transition metal ions bound to DNA. Reprints. (kt)