title: Substantial decrease of urinary 8-oxo-7,8-dihydroguanine, a product of the base excision repair pathway, in DNA glycosylase defective mice.
abstract: Genome integrity is maintained via removal (repair) of DNA lesions and an increased load of such DNA damage has been linked to numerous pathological conditions, including carcinogenesis and ageing. 8-Oxo-7,8-dihydroguanine is one of the most critical lesions of this type. The free 8-oxo-7,8-dihydroguanine produced by the action of a specific DNA glycosylase is a potential source of this compound in urine. To date, there has been no direct, experimental evidence demonstrating that urinary 8-oxo-7,8-dihydroguanine is produced by the base excision repair pathway. For clarification of this issue, we applied a recently developed methodology which involved high performance liquid chromatography pre-purification followed by gas chromatography with isotope dilution mass spectrometric detection to compare the urinary excretion rate of 8-oxo-7,8-dihydroguanine in wild type and OGG1 glycosylase knock out mice. Our study revealed a 26% reduction in urinary level of 8-oxo-7,8-dihydroguanine in OGG1 deficient mice in comparison with the wild type strain. This clearly indicates that the mouse OGG1 glycosylase contributes significantly to the generation of urinary 8-oxo-7,8-dihydroguanine. Therefore, urinary measurements of 8-oxo-7,8-dihydroguanine may be attributed to DNA damage and repair, which in turn suggests that they may be useful in studying associations between DNA repair and disease.
authors.affiliation: Department of Clinical Biochemistry, The Ludwik Rydygier Medical University in Bydgoszcz, Karlowicza 24, 85-092 Bydgoszcz, Poland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Rozalski
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Siomek
authors.forename: Daniel
authors.initials: D
authors.lastname: Gackowski
authors.forename: Marek
authors.initials: M
authors.lastname: Foksinski
authors.forename: Christine
authors.initials: C
authors.lastname: Gran
authors.forename: Arne
authors.initials: A
authors.lastname: Klungland
authors.forename: Ryszard
authors.initials: R
authors.lastname: Olinski
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage / Q000502:physiology; D045647:DNA Glycosylases / Q000172:deficiency / Q000502:physiology*; D004260:DNA Repair; D008401:Gas Chromatography-Mass Spectrometry; D006147:Guanine / Q000031:analogs & derivatives* / Q000652:urine; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: C024829:8-hydroxyguanine; D006147:Guanine; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse