Increased ROS generation in subsets of OGG1 knockout fibroblast cells.


Oxoguanine DNA glycosylase (OGG1) is a major base excision repair protein responsible for excision of the mutagenic 8-oxoguanosine (8-oxoG) lesions from the genome. Despite OGG1's importance, the moderate phenotype of Ogg1-null (Ogg1(-/-)) mice is not well understood. This study addresses a mechanism by which Ogg1(-/-) cells limit accumulation of 8-oxoG in their genome. Our data reveal that a subset of Ogg1(-/-) cells shows higher ROS levels ((H)ROS cells), while approximately 85% of Ogg1(-/-) cells exhibit physiological levels of ROS ((L)ROS cells). Ogg1(-/-) cells were sorted based on their DCF fluorescence intensity to obtain (L)ROS and (H)ROS cell cultures. (L)ROS cultures proliferated at a rate comparable to Ogg1(+/+) and gradually accumulated cells exhibiting increased ROS and 8-oxoG levels. (L)ROS cells show a 2.8-fold increase in 8-oxoG level vs. (H)ROS cells (7-27-fold). Mitochondria of (H)ROS cells released more H(2)O(2) than (L)ROS and Ogg1(+/+) cells and were eliminated by apoptotic-like processes. These findings suggest that in the absence of OGG1, a surveillance system is activated that removes cells with extreme 8-oxoG levels from Ogg1(-/-) cultures. Whether similar mechanisms exists in tissues of Ogg1(-/-) mice is the focus of future investigations.

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@article{Bacsi2007IncreasedRG, title={Increased ROS generation in subsets of OGG1 knockout fibroblast cells.}, author={Attila Bacsi and Grzegorz Chodaczek and Tapas K Hazra and David A . Konkel and Istvan Boldogh}, journal={Mechanisms of ageing and development}, year={2007}, volume={128 11-12}, pages={637-49} }