What are the Potential Sites of DNA Attack by N-Acetyl-p-benzoquinone Imine (NAPQI)?

Abstract

Metabolic bioactivation of small molecules can produce electrophilic metabolites that can covalently modify proteins and DNA. Paracetamol (APAP) is a commonly used over-the-counter analgesic, and its hepatotoxic side effects have been postulated to be due to the formation of the electrophilic metabolite N-acetylbenzoquinone imine (NAPQI). It has been established that NAPQI reacts to form covalent bonds to the side-chain functional groups of cysteine, methionine, tyrosine, and tryptophan residues. While there have been scattered reports that APAP can form adducts with DNA the nature of these adducts have not yet been fully characterised. Here the four deoxynucleosides, deoxyguanosine (dG), de..