Deoxyguanosine adducts of t-4-hydroxy-2-nonenal are endogenous DNA lesions in rodents and humans: detection and potential sources.
Cancer Res
; 60(6): 1507-11, 2000 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-10749113
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
DNA
/
Adutos de DNA
/
Desoxiguanosina
/
Aldeídos
Tipo de estudo:
Diagnostic_studies
/
Guideline
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article