Prophylaxis of oxidative DNA damage by formamidopyrimidine-DNA glycosylase.

Abstract

Lying at the gas-exchange interface, lung epithelia may be at risk of oxidation-induced mutagenesis. Further, inflammation processes possibly consequent on smoking liberate reactive oxygen species that multiply the carcinogenic effects of tobacco. DNA repair mechanisms play a major role in counteracting the deleterious effects of oxidative DNA damage. Some studies find positive associations between lung cancer and variations in the human 8-oxoguanine DNA glycosylase (hOGG1) gene that encodes a major DNA glycosylase for oxidized lesions with sluggish kinetics properties. The bacterial homologue formamidopyrimidine-DNA glycosylase (FPG) is 80-fold faster than hOGG1 in repairing mutagenic oxidative lesions. Cell-culture studies have shown that FPG can be expressed in mammalian cells, where it accelerates DNA repair and abates mutagenicity of a wide range of DNA-damaging agents. Prophylaxis of oxidative DNA damage and mutation could be achieved in lung epithelia and other tissues of at-risk individuals by expression of the FPG protein. Currently available vehicles for this peculiar type of gene therapy are briefly surveyed.

• Authors: Guido Frosina
• Journal: International journal of cancer (Int J Cancer) Vol. 119 Issue 1 Pg. 1-7 (Jul 01 2006) ISSN: 0020-7136 [Print] United States
• PMID: 16432839 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Escherichia coli Proteins
• Reactive Oxygen Species
• DNA Glycosylases
• oxoguanine glycosylase 1, human
• DNA-Formamidopyrimidine Glycosylase
• DNA-formamidopyrimidine glycosylase, E coli

Topics

• Adenoviridae
• Animals
• Cell Culture Techniques
• DNA Damage (drug effects)
• DNA Glycosylases (genetics)
• DNA Repair (drug effects)
• DNA-Formamidopyrimidine Glycosylase (metabolism)
• Dependovirus
• Escherichia coli Proteins (metabolism)
• Genetic Vectors
• Humans
• Lung (metabolism)
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)
• Respiratory Mucosa (metabolism)
• Retroviridae
• Smoking (adverse effects, metabolism)