Synthesis of N-2-(4-hydroxyphenyl)-2'-deoxyguanosine 3'-phosphate: Comparison by P-32-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 N-2-(4-hydroxyphenyl)guanosine 3'-phosphate. P-32-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 N-2-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 N-2-(4-hydroxyphenyl)-2'-deoxyguanosine 3'-phosphate. Using P-32-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 M(2)-(4-hydroxyphenyl)2'-deoxyguanosine 3'-phosphate.