Title: Synthesis of N2-(4-hydroxyphenyl)-2'-deoxyguanosine 3'-phosphate: comparison by 32P-postlabeling with the DNA adduct formed in HL-60 cells treated with hydroquinone.

Authors: Pongracz, K; Bodell, W J

Published In Chem Res Toxicol, (1996 Apr-May)

Abstract: A new adduct has been isolated from the reaction of guanosine 3'-phosphate and p-benzoquinone. The structure of this adduct has been determined as N2-(4-hydroxyphenyl)-guanosine 3'-phosphate. 32P-Postlabeling showed that this adduct is similar to the DNA adduct formed in HL-60 cells treated with hydroquinone. For comparison with the corresponding deoxyribonucleotide, a synthetic procedure was developed for the preparation of N2-substituted derivatives of 2'-deoxyguanosine 3'-phosphate. 2-Bromo-2'-deoxyinosine 3'-phosphate was synthesized with a combination of synthetic and enzymatic methods. Reaction of 2-bromo-2'-deoxyinosine 3'-phosphate with 4-hydroxyaniline gave N2-(4-hydroxyphenyl)-2'-deoxyguanosine 3'-phosphate. Using 32P-postlabeling, we compared this product with the DNA adduct produced in HL-60 cells treated with hydroquinone. The results of these studies suggest that the DNA adduct formed in HL-60 cells treated with hydroquinone corresponds to N2-(4-hydroxyphenyl)-2'-deoxyguanosine 3'-phosphate.

PubMed ID: 8728503

MeSH Terms: Autoradiography; Benzoquinones/pharmacology; DNA Adducts/analysis*; Deoxyguanine Nucleotides/chemical synthesis*; HL-60 Cells/drug effects*; HL-60 Cells/metabolism; Humans; Hydrogen-Ion Concentration; Hydroquinones/metabolism; Hydroquinones/pharmacology*; Magnetic Resonance Spectroscopy/methods; Mutagens/metabolism; Mutagens/pharmacology*; Phosphorus Radioisotopes; Spectrophotometry, Ultraviolet