Formation of acrolein adducts with 2'-deoxyadenosine in calf thymus DNA

Acrolein is a ubiquitous environmental contaminant that has been found to be mutagenic in prokaryotic and eukaryotic cells. In the present study, we examined the reactions of acrolein with 2'-deoxyadenosine and calf thymus single- and double-stranded DNA in aqueous buffered solutions at physiological conditions. The deoxynucleoside adducts were isolated by reversed-phase liquid chromatography, and their structures were determined by their UV absorbance, mass spectrometry, and 1H and 13C NMR spectroscopy. The reaction of 2'-deoxyadenosine with acrolein resulted in the formation of four structurally different adducts (dAI, dAII, dAIII, dAIV). The structures of the novel acrolein adducts, dAIII and dAIV, were assigned as 3-[N(6)-(2'-deoxyadenosinyl)]propanal (dAIII) and 9-(2'-deoxyribosyl-6-(3-formyl-1,2,5,6-tetrahydropyridyl)purine (dAIV), respectively. The adduct dAIII was found to arise via a Dimroth rearrangement of adduct dAI, while the adduct dAIV was shown to be formed upon further reaction of acrolein with dAIII. In the reaction of acrolein with calf thymus DNA, all studied 2'-deoxyadenosine-acrolein adducts were observed. For the first time, it is shown that the N(6)-adduct and the adducts which are derived from two acrolein units are formed in calf thymus DNA.