An Oxidized Abasic Lesion as an Intramolecular Source of DNA Adducts.
5'-(2-Phosphoryl-1,4-dioxobutane) (DOB) is a lesion produced in DNA via a variety of damaging agents. The DOB lesion spontaneously generatescis- andtrans-but-2-en-1,4-dial (1) via β-elimination.Cis- andtrans-but-2-en-1,4-dial forms exocyclic adducts with nucleosides. We used chemically synthesized DNA containing tritiated DOB incorporated at defined sites to examine the reactivity ofcis- andtrans-but-2-en-1,4-dial. Although the local DNA sequence does not appear to influence the distribution of nucleoside adducts, we find that DOB generates relatively high yields ofcis- andtrans-but-2-en-1,4-dial nucleoside adducts that likely are promutagenic.
Department of Chemistry, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA.
Lirui
L
Guan
Department of Chemistry, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD 21218, USA.
Marc M
MM
Greenberg