Accumulation of the Oxidative Base Lesion 8-Hydroxyguanine in DNA of Tumor-Prone Mice Defective in Both the Myh and Ogg1 DNA Glycosylases
MT Russo, G De Luca, P Degan, E Parlanti, E Dogliotti… - Cancer research, 2004 - AACR
MT Russo, G De Luca, P Degan, E Parlanti, E Dogliotti, DE Barnes, T Lindahl, H Yang…
Cancer research, 2004•AACRAbstract The OGG1 and MYH DNA glycosylases prevent the accumulation of DNA 8-
hydroxyguanine. In Myh−/− mice, there was no time-dependent accumulation of DNA 8-
hydroxyguanine in brain, small intestine, lung, spleen, or kidney. Liver was an exception to
this general pattern. Inactivation of both MYH and OGG1 caused an age-associated
accumulation of DNA 8-hydroxyguanine in lung and small intestine. The effects of abrogated
OGG1 and MYH on hepatic DNA 8-hydroxyguanine levels were additive. Because there is …
hydroxyguanine. In Myh−/− mice, there was no time-dependent accumulation of DNA 8-
hydroxyguanine in brain, small intestine, lung, spleen, or kidney. Liver was an exception to
this general pattern. Inactivation of both MYH and OGG1 caused an age-associated
accumulation of DNA 8-hydroxyguanine in lung and small intestine. The effects of abrogated
OGG1 and MYH on hepatic DNA 8-hydroxyguanine levels were additive. Because there is …
Abstract
The OGG1 and MYH DNA glycosylases prevent the accumulation of DNA 8-hydroxyguanine. In Myh−/− mice, there was no time-dependent accumulation of DNA 8-hydroxyguanine in brain, small intestine, lung, spleen, or kidney. Liver was an exception to this general pattern. Inactivation of both MYH and OGG1 caused an age-associated accumulation of DNA 8-hydroxyguanine in lung and small intestine. The effects of abrogated OGG1 and MYH on hepatic DNA 8-hydroxyguanine levels were additive. Because there is an increased incidence of lung and small intestine cancer in Myh−/−/Ogg1−/− mice, these findings support a causal role for unrepaired oxidized DNA bases in cancer development.
AACR