Assays for the Repair of Oxidative Damage by Formamidopyrimidine Glycosylase (Fpg) and 8-)Oxoguanine DNA Glycosylase (OGG-1)

Oxidative damage produced by endogenously and exogenously generated reactive oxygen species (ROS) has been implicated in mutagenesis and carcinogenesis and may play an important role in the pathogenesis of aging (1 ). Among ROS, the hydroxyl radical is highly reactive, producing a variety of purine- and pyrimidine-derived lesions in DNA (2 ,3 ). A major pathway of hydroxyl radical-induced DNA damage involves attack on the C8 position of purines to produce 8-oxoG (7,8-dihydro-8-oxoguanine), 8-oxoA (7,8,-dihydro-8-oxoadenine) and imidazole ring fragmented lesions (formamidopyrimidines [2 ,4 ]). There is strong evidence to suggest that the 8-oxoG lesion, which is produced in abundance, is highly mutagenic in vitro and in vivo (5 ,6 ). Such oxidized purines are primarily repaired by the base excision repair pathway, the initial step of which is excision of the modified base by DNA glycosylases (7 ,8 ).