Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 133, Issue 24, Pages 9140-9143Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja2004686
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Funding
- FAPESP (Fundacao de Amparo a Pesquisa do Estado de sao Paulo)
- CNPq (Conselho Nacional para o Desenvolvimento Cientifico e Tecnologico)
- CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)
- INCT de Processos Redox em Biomedicina - Redoxoma
- Pro-Reitoria de Pesquisa da USP
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Acetaldehyde is an environmentally widespread genotoxic aldehyde present in tobacco smoke, vehicle exhaust and several food products. Endogenously, acetaldehyde is produced by the metabolic oxidation of ethanol by hepatic NAD-dependent alcohol dehydrogenase and during threonine catabolism. The formation of DNA adducts has been regarded as a critical factor in the mechanisms of acetaldehyde mutagenicity and carcinogenesis. Acetaldehyde reacts with 2'-deoxyguanosine in DNA to form primarily N-2-ethylidene-2'-deoxyguanosine. The subsequent reaction of N-2-ethylidenedGuo with another molecule of acetaldehyde gives rise to 1,N-2-propano-2'-deoxyguanosine (1,N-2-propanodGuo), an adduct also found as a product of the crotonaldehyde reaction with dGuo. However, adducts resulting from the reaction of more than one molecule of acetaldehyde in vivo are still controversial. In this study, the unequivocal formation of 1,N-2-propanodGuo by acetaldehyde was assessed in human cells via treatment with [C-13(2)]-acetaldehyde. Detection of labeled 1,N-2-propanodGuo was performed by HPLC/MS/MS. Upon acetaldehyde exposure (703 mu M), increased levels of both 1,N-2-etheno-2'-deoxyguanosine (1,N-2-epsilon dGuo), which is produced from alpha,beta-unsaturated aldehydes formed during the lipid peroxidation process, and 1,N-2-propanodGuo were observed. The unequivocal formation of 1,N-2-propanodGuo in cells exposed to this aldehyde can be used to elucidate the mechanisms associated with acetaldehyde exposure and cancer risk.
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