Etheno Adducts

Helmenstine A.M., Li Y.S., Vo-Dinh T., Surface-enhanced Raman-scattering analysis of etheno adducts of adenine, Vibrational Spectrosc. 1993 4 359-364. 

I IL / Substituted ethano or etheno adducts H N (HNE-dGuo adducts, HNE-dAdo adduci... 

Bromo- and chloroacetaldehyde react readily with adenine and cytosine, either free or as constituents of nucleosides and nucleotides (Figure 5)63. The etheno adducts so formed are highly fluorescent, a discovery that has made this reaction a very valuable research... 

FIGURE 5. The mehanism for the formation of etheno adducts by the reaction of chloroacetaldehyde and base components of nucleic acids. Structures of -adenosine and e-cytidine... 

Figure 22.7. The major DNA lesions of the lipid peroxidation products. (A) DNA lesions produced by malondialdehyde. Mi denotes the monomeric form of malondialdehyde. Malo-ndialdehyde can polymerize to form dimers and trimers that can also react with DNA. The resulting lesions are designated as M2 and M3, respectively (c.g., M2G). These lesions, however, may not be significant in cells as polymerization of malondialdehyde is relatively slow at neutral pH. (B) The l,7V2-propano-dG DNA adducts produced by acrolein, crotonaldehyde, and 4-hydroxy-2-nonenal (HNE). Stereochemistry is not shown. The l.A -acrolcin-dG consists of three isomers. The 1, AAcrotonaldchyde-dG consists of two isomers. The FAAlINF-dGconsistsof four isomers. (C)EthenoDNAadductsproduced by 2,3-epoxy-4-hydroxynonenal. Further oxidation of 4-hydroxynonenal produces 2,3-epoxy-4-hydroxynonenal, which reacts with DNA to form the exocyclic etheno adducts.

The major aldehyde products of lipid peroxidation are malon-dialdehyde and 4-hydroxynonenal (Table 1, Fig. 4). Malondi-aldehyde can react with DNA to generate adducts at the bases A, C, and G. The mutagenic adduct MIG (pyrimido(l,2-a)purin-10(3H)one) has been detected at levels as high as 1 adduct per 10 nucleosides in human tissues. MIG is a reactive electrophile that can undergo further modification, leading to crosslinking of an adducted DNA strand to the opposite strand, or to some protein (22). Exocyclic etheno adducts can also arise from lipid peroxidation, possibly by reaction of an epoxide of 4-hydroxynonenal with A, C, or G in DNA. 

Figure 4 (a) Maionaidehyde is a major product of iipid peroxidation that is reactive with A, G, and C in DNA. (b) 4-Hydroxynonenai, another major product of iipid peroxidation, can generate exocyciic etheno adducts of A, C, and G in DNA. (Reproduced from Reference 1 with permission.)... 

Nair J, Gal A, Tamir S, Tannenbaum SR, Wogan GN and Bartsch H, Etheno adducts in spleen DNA of SJL mice stimulated to overproduce nitric oxide. Carcinogenesis 19(12) 2081-4, 1998. 

Figure 2.8 Lipid peroxidation-derived etheno adducts.

Lee and Blair provided a critical link from lipid peroxidation to the formation of etheno adducts by demonstrating the reactivity of 4-hydroperoxy-2-nonenal, 4-oxo-2-nonenal, and 4,5-epoxy-2-decenal with nucleosides. Both 4-hydroperoxy-... 

Implicit in the discussion of the chemistry of formation for DNA adducts in vitro is the generation of DNA adducts in vivo. The previously described pyrimidopuri-none, propano, and etheno adducts are found in human tissue samples and cultured human cell lines. The estimated levels of these adducts range from one to 10 adducts/108 bp DNA. Owing to the relatively low abundance of these lesions amid a preponderance of impurities, highly sensitive and specific analytical... 

The third type of oxidative damage that can occur in DNA would result from the addition of bifunctional electrophiles (4-hydroxy-2-nonenal and 4-oxo-2-none-nal) that result from lipid peroxidation to the nucleobases. The etheno adducts formed with 4-hydroxy-2-nonenal can also be derived from vinyl chloride however, the heptano-etheno adducts derived from 4-oxo-2-nonenal can only be derived from lipid peroxidation [115], Thus far no attempt has been made to measure these adducts as a result of the AKR pathway of PAH activation. 

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