Accumulation of the oxidative base lesion 8-hydroxyguanine in DNA of tumor-prone mice defective in both the Myh and Ogg1 DNA glycosylases.
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.
Russo
Maria Teresa
MT
Department of Environment and Primary Prevention, Istituto Superiore di Sanita', Rome, Italy.
De Luca
Gabriele
G
Degan
Paolo
P
Parlanti
Eleonora
E
Dogliotti
Eugenia
E
Barnes
Deborah E
DE
Lindahl
Tomas
T
Yang
Hanjing
H
Miller
Jeffrey H
JH
Bignami
Margherita
M
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
C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; C061738:mutY adenine glycosylase