Formation of deoxyguanosine cross-links from calf thymus DNA treated with acrolein and 4-hydroxy-2-nonenal.
Chem Res Toxicol
; 23(11): 1701-13, 2010 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-20964440
ABSTRACT
Acrolein (AC) and 4-hydroxy-2-nonenal (HNE) are endogenous bis-electrophiles that arise from the oxidation of polyunsaturated fatty acids. AC is also found in high concentrations in cigarette smoke and automobile exhaust. These reactive α,ß-unsaturated aldehyde (enal) covalently modify nucleic acids, to form exocyclic adducts, where the three-carbon hydroxypropano unit bridges the N1 and N(2) positions of deoxyguanosine (dG). The bifunctional nature of these enals allows them to undergo reaction with a second nucleophilic group and form DNA cross-links. These cross-linked enal adducts are likely to contribute to the genotoxic effects of both AC and HNE. We have developed a sensitive mass spectrometric method to detect cross-linked adducts of these enals in calf thymus DNA (CT DNA) treated with AC or HNE. The AC and HNE cross-linked adducts were measured by the stable isotope dilution method, employing a linear quadrupole ion trap mass spectrometer and consecutive reaction monitoring at the MS(3) or MS(4) scan stage. The lower limit of quantification of the cross-linked adducts is â¼1 adduct per 10(8) DNA bases, when 50 µg of DNA is assayed. The cross-linked adducts occur at levels that are â¼1-2% of the levels of the monomeric 1,N(2)-dG adducts in CT DNA treated with either enal.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Acroleína
/
DNA
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Desoxiguanosina
/
Aldeídos
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article