title: Accumulation of the oxidative base lesion 8-hydroxyguanine in DNA of tumor-prone mice defective in both the Myh and Ogg1 DNA glycosylases.
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.
authors.affiliation: Department of Environment and Primary Prevention, Istituto Superiore di Sanita', Rome, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Russo
authors.forename: Gabriele
authors.initials: G
authors.lastname: De Luca
authors.forename: Paolo
authors.initials: P
authors.lastname: Degan
authors.forename: Eleonora
authors.initials: E
authors.lastname: Parlanti
authors.forename: Eugenia
authors.initials: E
authors.lastname: Dogliotti
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Barnes
authors.forename: Tomas
authors.initials: T
authors.lastname: Lindahl
authors.forename: Hanjing
authors.initials: H
authors.lastname: Yang
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Miller
authors.forename: Margherita
authors.initials: M
authors.lastname: Bignami
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D045647:DNA Glycosylases / Q000172:deficiency* / Q000235:genetics; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism*; D007421:Intestine, Small / Q000201:enzymology / Q000378:metabolism; D008168:Lung / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; C061738:mutY adenine glycosylase