Deoxyguanosine adducts of t-4-hydroxy-2-nonenal are endogenous DNA lesions in rodents and humans: detection and potential sources.
t-4-Hydroxy-2-nonenal (HNE) is a free radical-mediated oxidation product of polyunsaturated fatty acids. As an electrophile, HNE readily binds to proteins and yields diastereomeric cyclic 1,N2-propano adducts with deoxyguanosine (dG). Here, we report the detection and identification of the HNE-derived cyclic 1,N2-propano-dG adducts as endogenous DNA lesions in tissues of untreated rats and humans using a highly sensitive 32P-postlabeling method in conjunction with high-performance liquid chromatography. These adducts were first verified by their comigration with the synthetic UV standards of HNE-dG adducts. Subsequently, their identities were unequivocally established by two independent reactions. An approximately 37-fold increase in the levels of HNE-dG adducts was observed in the liver DNA of F344 rats after treatment with CCl4, suggesting that tissue lipid peroxidation is a likely source of their formation. Our studies in vitro further indicate that omega-6 polyunsaturated fatty acids are likely a unique class of fatty acids involved in HNE-dG adduct formation.
Chung
F L
FL
Division of Carcinogenesis and Molecular Epidemiology, American Health Foundation, Valhalla, New York 10595, USA. chungahf@aol.com
Nath
R G
RG
Ocando
J
J
Nishikawa
A
A
Zhang
L
L
D000447:Aldehydes / Q000737:chemistry*; D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003106:Colon / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D018736:DNA Adducts / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D003849:Deoxyguanosine / Q000737:chemistry*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D000447:Aldehydes; D018736:DNA Adducts; D004247:DNA; D002251:Carbon Tetrachloride; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal