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dc.contributor.authorHarrison, Kathryn L
dc.contributor.authorJukes, Rebekah
dc.contributor.authorCooper, Donald P
dc.contributor.authorShuker, David E
dc.date.accessioned2010-01-28T13:47:23Z
dc.date.available2010-01-28T13:47:23Z
dc.date.issued1999-01
dc.identifier.citationDetection of concomitant formation of O6-carboxymethyl- and O6-methyl-2'-deoxyguanosine in DNA exposed to nitrosated glycine derivatives using a combined immunoaffinity/HPLC method. 1999, 12 (1):106-11 Chem. Res. Toxicol.en
dc.identifier.issn0893-228X
dc.identifier.pmid9894025
dc.identifier.doi10.1021/tx980057n
dc.identifier.urihttp://hdl.handle.net/10541/90767
dc.description.abstractA previous observation that an N-nitroso-N-carboxymethyl derivative reacts with DNA to give both O6-carboxymethyl-2'-deoxyguanosine (O6-CMdGuo) and O6-methyl-2'-deoxyguanosine (O6-MedGuo) [Shuker, D. E. G., and Margison, G. P. (1997) Cancer Res. 57, 366-369] has been confirmed using a range of nitrosated glycine derivatives [N-acetyl-N'-nitroso-N'-prolylglycine (APNG), azaserine (AS), and potassium diazoacetate (KDA)]. In addition, mesyloxyacetic acid (MAA) was also found to give both O6-adducts in DNA. O6-CMdGuo and O6-MedGuo were assessed in enzymatic hydrolysates of treated calf thymus DNA using a combined immunoaffinity/HPLC/fluorescence procedure. The ratio of O6-CMdGuo to O6-MedGuo varied somewhat between the different compounds with APNG giving the most methylation (O6-CM:O6-Me ratio of 10) and AS the least (39), with KDA and MAA giving intermediate amounts (16 and 18, respectively). The formation of O6-MedGuo by the four compounds probably arises through decarboxylation at various stages in the decomposition pathways, but the exact mechanisms remain to be clarified. The formation of O6-MedGuo from reactions of nitrosated glycine derivatives with DNA in vitro may explain the frequent detection of this adduct in human gastrointestinal DNA, as nitrosation of dietary glycine may occur. O6-CMdGuo is likely to be a useful biomarker of this pathway in vivo and has been detected in human tissues.
dc.language.isoenen
dc.subject.meshAnimals
dc.subject.meshCalibration
dc.subject.meshCarcinogens
dc.subject.meshCattle
dc.subject.meshChromatography, Affinity
dc.subject.meshChromatography, High Pressure Liquid
dc.subject.meshDNA
dc.subject.meshDNA Adducts
dc.subject.meshDeoxyguanosine
dc.subject.meshGlycine
dc.subject.meshImmunosorbents
dc.subject.meshNitroso Compounds
dc.subject.meshThymus Gland
dc.titleDetection of concomitant formation of O6-carboxymethyl- and O6-methyl-2'-deoxyguanosine in DNA exposed to nitrosated glycine derivatives using a combined immunoaffinity/HPLC method.en
dc.typeArticleen
dc.contributor.departmentMRC Toxicology Unit, Hodgkin Building, University of Leicester, P.O. Box 138, Lancaster Road, Leicester LE1 9HN, U.K.en
dc.identifier.journalChemical Research in Toxicologyen
html.description.abstractA previous observation that an N-nitroso-N-carboxymethyl derivative reacts with DNA to give both O6-carboxymethyl-2'-deoxyguanosine (O6-CMdGuo) and O6-methyl-2'-deoxyguanosine (O6-MedGuo) [Shuker, D. E. G., and Margison, G. P. (1997) Cancer Res. 57, 366-369] has been confirmed using a range of nitrosated glycine derivatives [N-acetyl-N'-nitroso-N'-prolylglycine (APNG), azaserine (AS), and potassium diazoacetate (KDA)]. In addition, mesyloxyacetic acid (MAA) was also found to give both O6-adducts in DNA. O6-CMdGuo and O6-MedGuo were assessed in enzymatic hydrolysates of treated calf thymus DNA using a combined immunoaffinity/HPLC/fluorescence procedure. The ratio of O6-CMdGuo to O6-MedGuo varied somewhat between the different compounds with APNG giving the most methylation (O6-CM:O6-Me ratio of 10) and AS the least (39), with KDA and MAA giving intermediate amounts (16 and 18, respectively). The formation of O6-MedGuo by the four compounds probably arises through decarboxylation at various stages in the decomposition pathways, but the exact mechanisms remain to be clarified. The formation of O6-MedGuo from reactions of nitrosated glycine derivatives with DNA in vitro may explain the frequent detection of this adduct in human gastrointestinal DNA, as nitrosation of dietary glycine may occur. O6-CMdGuo is likely to be a useful biomarker of this pathway in vivo and has been detected in human tissues.


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