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 byFAPESP:2011/10048-5, CAPES, INCT Redoxoma:573530/2008-4,NAP Redoxoma: 2011.1.9352.1.8, CEPID Redoxoma:2013/07937-8. [ABSTRACT FROM AUTHOR]