Prophylaxis of oxidative DNA damage by formamidopyrimidine-DNA glycosylase.
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.
Frosina
Guido
G
Department of Translational Oncology, Experimental Oncology B laboratory, Istituto Nazionale Ricerca Cancro, Genova, Italy. guido.frosina@istge.it
D000256:Adenoviridae; D000818:Animals; D018929:Cell Culture Techniques; D004249:DNA Damage / Q000187:drug effects*; D045647:DNA Glycosylases / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects; D043382:DNA-Formamidopyrimidine Glycosylase / Q000378:metabolism*; D000229:Dependovirus; D029968:Escherichia coli Proteins / Q000378:metabolism; D005822:Genetic Vectors; D006801:Humans; D008168:Lung / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism; D012190:Retroviridae; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism
D029968:Escherichia coli Proteins; D017382:Reactive Oxygen Species; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D043382:DNA-Formamidopyrimidine Glycosylase; C468610:DNA-formamidopyrimidine glycosylase, E coli