The N7-glycidamide adduct of 2′-deoxyguanosine on the template strand induces DNA replication inhibition and mutagenesis in human cells

Abstract

We examined genotoxic potential of N7-glycidamide adduct of 2′-deoxyguanosine (dG) (GA⁷dG) by using its stable analogue, GA⁷FdG. Replication efficiency of a shuttle vector carrying GA⁷FdG was about half of FdG control vector in human cells. In the GA⁷FdG strand progeny, base substitution mutations and single base deletions were observed. We then further revealed that GA⁷FdG on the template DNA strongly inhibit DNA polymerase activity. These results suggest that GA⁷dG in genomic DNA induces DNA replication inhibition and mutagenesis, and thus contributes to acrylamide-induced genotoxicity.