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.
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.
Pongracz
K
K
Department of Neurological Surgery, School of Medicine, University of California, San Francisco 94143, USA.
Bodell
W J
WJ
D001345:Autoradiography; D016227:Benzoquinones / Q000494:pharmacology; D018736:DNA Adducts / Q000032:analysis*; D003848:Deoxyguanine Nucleotides / Q000138:chemical synthesis*; D018922:HL-60 Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006873:Hydroquinones / Q000378:metabolism / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009153:Mutagens / Q000378:metabolism / Q000494:pharmacology*; D010761:Phosphorus Radioisotopes; D013056:Spectrophotometry, Ultraviolet
D016227:Benzoquinones; D018736:DNA Adducts; D003848:Deoxyguanine Nucleotides; D006873:Hydroquinones; D009153:Mutagens; C101061:N(2)-(4-hydroxyphenyl)-2'-deoxyguanosine 3'-phosphate; D010761:Phosphorus Radioisotopes; C004532:quinone; C031927:hydroquinone