Novel molecular targets for risk identification: DNA repair enzyme activities

Oxidized guanine lesions and hOgg1 activity in lung cancer

“…One recent knockout study showed that loss of hOgg1 protein function predisposed mice to lung adenocarcinoma development (Sakumi et al, 2003). In humans, low hOgg1 levels in peripheral lymphocytes appeared to convey an increased risk of lung cancer development in smokers (Paz-Elizur et al, 2003). These findings support the notion that defects in hOGG1 and 8-oxoG repair may play an important step in tumorigenesis.…”

“…Recent studies (Paz-Elizur et al, 2003) showed that hOgg1 activity was lower in peripheral blood mononuclear cells from patients with non-small-cell lung cancer than in those from control subjects. Paz-Elizur et al (2003) studies provided evidence for defective repair of 8-oxoG in lung cancer patients suggesting perhaps that the lung cancer cells may be defective in 8-oxoG repair. To date, there are limited studies that have examined the repair of this mutagenic lesion in lung cancer cells.…”

“…Previous studies have shown that lung cancer tissue harbored higher levels of oxidatively induced DNA lesions than cancer-free surrounding tissue (Olinski et al, 1992;Jaruga et al, 1994), suggesting a possible defect in the repair of these lesions. Recently, low hOgg1 activity was shown to be significantly associated with an increased risk of nonsmall-cell lung cancer (Paz-Elizur et al, 2003). Other recent studies (Xie et al, 2004) showed that deficiencies in both myh and ogg1 in mice resulted in lung tumor predisposition and G to T mutations in activating hot spot codon 12 of K-ras oncogene in lung tumors.…”

Tumor Suppression by DNA Base Excision Repair

“…The smoking status may elevate in human cells the level of oxidative damage that, in turn, may contribute to tobaccoinduced carcinogenesis. Importantly, an association between low hOGG1 activity and risk of lung cancer has been described [126]. Substantial variations in the statistical power of this kind of studies can be observed in the literature, with the number of recruited patients ranging in one order of magnitude.…”

Foreword

“…In a paper published in this issue [2], Dr. Livneh described a new paradigm to risk assessment is being developed through the use of functional assays of critical cellular components that ensure the fidelity of key control systems. DNA repair may be one of these systems.…”