biostudies-literatureChang SCNCRR NIH HHSHoward Hughes Medical InstituteNIEHS NIH HHSNCI NIH HHSNIGMS NIH HHS5489-500https://www.ebi.ac.uk/biostudies/studies/S-EPMC4477646biostudies-literatureUnknown43(11)Etheno DNA adducts are a prevalent type of DNA damage caused by vinyl chloride (VC) exposure and oxidative stress. Etheno adducts are mutagenic and may contribute to the initiation of several pathologies; thus, elucidating the pathways by which they induce cellular transformation is critical. Although N(2),3-ethenoguanine (N(2),3-εG) is the most abundant etheno adduct, its biological consequences have not been well characterized in cells due to its labile glycosidic bond. Here, a stabilized 2'-fluoro-2'-deoxyribose analog of N(2),3-εG was used to quantify directly its genotoxicity and mutagenicity. A multiplex method involving next-generation sequencing enabled a large-scale in vivo analysis, in which both N(2),3-εG and its isomer 1,N(2)-ethenoguanine (1,N(2)-εG) were evaluated in various Nucleic acids researchNext-generation sequencing reveals the biological significance of the N(2),3-ethenoguanine lesion in vivo.PMC4477646S10 RR019022P01 CA160032P30 ES000267P01 ES005355P01 CA026731P30 ES002109R01 CA080024R01 ES010546T32 ES007020R01 GM069857R37 CA080024P30 CA068485P01 ES05355Marnett LJChang SCWu JYau EFedeles BILi DRizzo CJChristov PPJost MLevine SSZhao LDelaney JCEssigmann JMDrennan CLGuengerich FPSingh VfalseNext-generation sequencing reveals the biological significance of the N(2),3-ethenoguanine lesion in vivo.Etheno DNA adducts are a prevalent type of DNA damage caused by vinyl chloride (VC) exposure and oxidative stress. Etheno adducts are mutagenic and may contribute to the initiation of several pathologies; thus, elucidating the pathways by which they induce cellular transformation is critical. Although N(2),3-ethenoguanine (N(2),3-εG) is the most abundant etheno adduct, its biological consequences have not been well characterized in cells due to its labile glycosidic bond. Here, a stabilized 2'-fluoro-2'-deoxyribose analog of N(2),3-εG was used to quantify directly its genotoxicity and mutagenicity. A multiplex method involving next-generation sequencing enabled a large-scale in vivo analysis, in which both N(2),3-εG and its isomer 1,N(2)-ethenoguanine (1,N(2)-εG) were evaluated in various 2015-01-01T00:00:00Z2015 Jun2026-04-12T19:56:55.571Z2019-03-27T01:53:54ZS-EPMC44776462583799210.1093/nar/gkv243