Quantification of DNA adducts in lungs, liver and brain of rats exposed to acetaldehyde.

ABSTRACT

Air pollution is a major risk for human health. Acetaldehyde is an environmental pollutant present in tobacco smoke, vehicle exhaust and several food products. 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 primarily form N(2)-ethylidene-2'-deoxyguanosine (N(2)-ethylidene-dGuo). The subsequent reaction of N(2)-ethylidene-dGuo with another molecule of acetaldehyde gives rise to 1,N(2)-propano-2´-deoxyguanosine (1,N(2)-propanodGuo). In this study, on-line reverse-phase high-performance liquid chromatography (HPLC) separation with tandem mass spectrometry detection was utilized for the accurate quantification of 1,N(2)-propanodGuo and 1,N(2)-etheno-2'-deoxyguanosine (1,N(2)-edGuo) in tissues of rats exposed to 12 ppb, 33 ppb and 96 ppb acetaldehyde in atmospheric air for 50 days. A significant increase in the levels of 1,N(2)-propanodGuo was observed in lung tissues of rats exposed to 12 ppb (7.8/10(8) dGuo); 33 ppb (8.9/10(8) dGuo) and 96 ppb (11.6/10(8) dGuo) compared to controls (4.2/10(8) dGuo). For comparative purposes, the levels of 1,N(2)-etheno-2'-deoxyguanosine (1,N(2)-edGuo), which is produced from a,b-unsaturated aldehydes formed during the lipid peroxidation process were also measured. Elevated levels of 1,N(2)-edGuo were observed only in lung tissues of animals exposed to 96 ppb acetaldehyde. 1,N(2)-propanodGuo also differed quantitatively in liver but not in brain. The monitoring of 1,N(2)-propanodGuo levels in tissues provides important information on acetaldehyde genotoxicity and may contribute to the elucidation of the mechanisms associated with acetaldehyde exposure and cancer risk. Supported byFAPESP2011/10048-5, CAPES, INCT Redoxoma573530/2008-4,NAP Redoxoma 2011.1.9352.1.8, CEPID Redoxoma2013/07937-8.