DNA Repair Proteins as Molecular Therapeutics for Oxidative and Alkylating Lung Injury

Min      Wu

doi:10.2174/1566523053544245

Abstract

Endogenous and environmental oxidation is increasingly becoming an important factor associated with numerous disorders in both children and adults. The lung is particularly prone to oxidation, as the gas exchange organ is continuously exposed to a great deal of airborne oxidants. Lung oxidation-induced toxicity is a critical clinical problem that is currently lacking cure. For example, treatment for acute respiratory distress syndrome (ARDS), a common type of acute diffuse lung injury, is strictly supportive. Alkylating chemotherapeutics and many methyl chemicals can cause acute or chronic lung injury, which is also difficult to treat. Many new approaches are being tried to improve the treatment of lung oxidation and alkylation; one of these is the use of DNA repair proteins, such as base excision repair proteins that are largely involved in repairing DNA damage caused by oxidation and alkylation. Recent advances have revealed their promising potential for treating oxidation toxicity. Here we discuss discoveries that have led to this possibility, including pioneering research into the cellular signaling transduction and molecular mechanisms of DNA repair proteins. In conclusion, when combined with other therapeutic measures such as anti-oxidant chemicals and enzymes, DNA repair proteins may have great potential for treating acute and chronic lung toxicity induced by oxidation and alkylation.

Keywords: base excision dna repair, hyperoxia, gene therapy, oxidants, alkylating drugs, lung toxicity, acute respiratory distress syndrome, and chemotherapeutics