Role of 1,N2-propanodeoxyguanosine adducts as endogenous DNA lesions in rodents and humans.
Results obtained in a number of studies in vitro and in vivo support the hypothesis that short- and long-chain enals and their epoxides derived from oxidized polyunsaturated fatty acids are potential endogenous sources of cyclic propano and etheno DNA adducts. We previously reviewed the evidence from some of these studies. Here, we describe the results of our more recent studies on the role of 1,N2-propanodeoxyguanosine adducts as endogenous DNA lesions. These studies include: the detection of distinct patterns of such adducts in various tissues of different species; the detection of long-chain trans-4-hydroxynonenal-derived deoxyguanosine adducts in vivo; the specificity of the formation of enal-derived propano adducts from omega-3 and omega-6 polyunsaturated fatty acids; and the detection of acrolein- and crotonaldehyde-derived adducts in human oral tissue DNA and their increased levels in smokers. Taken together, these studies further strengthen the hypothesis that enals produced by lipid peroxidation are the primary source for cyclic propano adducts in vivo, but these results cannot rule out the possible contribution of environmental and other sources. The mutagenicity of enals and their epoxides and the results of site-specific mutagenesis studies indicate that the cyclic adducts are potential promutagenic lesions; however, only circumstantial evidence is currently available for their role in carcinogenesis.
Chung
F L
FL
Division of Carcinogenesis and Molecular Epidemiology, American Health Foundation, Valhalla, NY 10595, USA.
Zhang
L
L
Ocando
J E
JE
Nath
R G
RG
D000171:Acrolein / Q000032:analysis; D000447:Aldehydes / Q000032:analysis; D000818:Animals; D016718:Arachidonic Acid / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000187:drug effects; D018736:DNA Adducts / Q000032:analysis / Q000096:biosynthesis*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000633:toxicity; D005227:Fatty Acids / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D019787:Linoleic Acid / Q000633:toxicity; D015227:Lipid Peroxidation; D051379:Mice; D008956:Models, Chemical; D051381:Rats
D000447:Aldehydes; D018736:DNA Adducts; D005227:Fatty Acids; C060934:1,N(2)-propanodeoxyguanosine; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D000171:Acrolein; D004247:DNA; C012796:2-butenal; D019787:Linoleic Acid; D003849:Deoxyguanosine; D005978:Glutathione