Detection of concomitant formation of O6-carboxymethyl- and O6-methyl-2'-deoxyguanosine in DNA exposed to nitrosated glycine derivatives using a combined immunoaffinity/HPLC method.

Abstract	A 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.
Authors	K L Harrison, R Jukes, D P Cooper, D E Shuker
Journal	Chemical research in toxicology (Chem Res Toxicol) Vol. 12 Issue 1 Pg. 106-11 (Jan 1999) ISSN: 0893-228X [Print] United States
PMID	9894025 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Carcinogens DNA Adducts Immunosorbents Nitroso Compounds O(6)-(carboxymethyl)-2'-deoxyguanosine DNA O(6)-methyl-2'-deoxyguanosine Deoxyguanosine Glycine
Topics	Animals Calibration Carcinogens (chemistry) Cattle Chromatography, Affinity Chromatography, High Pressure Liquid DNA (chemistry) DNA Adducts (analysis) Deoxyguanosine (analogs & derivatives, chemistry) Glycine (chemistry) Immunosorbents Nitroso Compounds (chemistry) Thymus Gland (chemistry)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!