Methods for determining and agents for modulating cellular redox potential and genotoxic states

摘要

Methods for determining the genotoxic or carcinogenic status of a subject by analyzing the cellular redox potential of a test specimen where an increased risk of, or presence of, genotoxic injury or cancer is indicated when the cellular redox potential favors oxidatively derived modified nucleotide bases. A sensitive method is disclosed wherein DNA is isolated from a test specimen obtained from a test subject and assayed for modified nucleotide bases that have formed either stable reductively formed derivatives or stable oxidatively formed derivatives. By identifying and comparing those modified nucleotide bases derived via reductive pathways to those modified nucleotide bases derived via oxidative pathways, a determination as to the cancer status of the test specimen can be made wherein a greater cancerous state exists when the ratio between the two species of modified nucleotide bases indicates that oxidatively formed derivative are favored over reductively formed derivatives. Also disclosed are methods for modulating the cellular redox potential so as to decrease the likelihood of oxidatively derived modified base formation and cancer formation. Methods for monitoring the efficacy of such therapy are additionally disclosed.