Genotoxic Assessment of DNA and Cellular Fractions from Cancerous Tissues: APrognostic Assay for Cancer Risk

摘要

Factors that elicit mutagenic damage to the DNA have been intensely studied forover 50 years. These reactions include the introduction of bulky substituents on the DNA bases which are products of two-electron oxidations (1). Recent studies on these DNA changes suggest that they are more prone to blocking DNA replication and transcription than creating mutagenic lesions (2). A second means of creating potentially mutagenic changes to the DNA is through one-electron, radical-induced oxidative modifications of the nucleotide bases (3). One such free radical is the hydroxyl radical, eOH. The .011 is likely generated in vivo from 11202 in a Fe++-catalyzed Fenton reaction (4, 5). The source of 11202 may be through cytochrome P-450 oxidoreductase cycling after exposure of the tissue to various types of endogenous and exogenous chemicals (6). In fact, those chemicals capable of forming bulky adducts with DNA through two-electron oxidations also form one or more moles of 11202 per mole of bulky adduct. Thus, both processes occur simultaneously. Historically, it has been routinely possible to identify and measure the incidence of the bulky adducts by means of techniques such as 32P-postlabeling analysis (7). pg 4. JMD.