| Online-Ressource |
Verfasst von: | Nair, Jagadeesan [VerfasserIn]  |
| Fürstenberger, Gerhard [VerfasserIn]  |
| Bürger, Friederike [VerfasserIn]  |
| Marks, Friedrich [VerfasserIn]  |
| Bartsch, Helmut [VerfasserIn]  |
Titel: | Promutagenic etheno−DNA adducts in multistage mouse skin carcinogenesis |
Titelzusatz: | Correlation with Lipoxygenase-Catalyzed Arachidonic Acid Metabolism |
Verf.angabe: | Jagadeesan Nair, Gerhard Fürstenberger, Friederike Bürger, Friedrich Marks, and Helmut Bartsch |
E-Jahr: | 2000 |
Jahr: | July 8, 2000 |
Umfang: | 7 S. |
Fussnoten: | Gesehen am 28.01.2021 |
Titel Quelle: | Enthalten in: Chemical research in toxicology |
Ort Quelle: | New York, NY : ACS Publ., 1988 |
Jahr Quelle: | 2000 |
Band/Heft Quelle: | 13(2000), 8, Seite 703-709 |
ISSN Quelle: | 1520-5010 |
Abstract: | Formation of the lipoxygenase-catalyzed metabolites of arachidonic acid, 8-hydroxyeicosatetraenoic acid (8-HETE) and 12-hydroxyeicosatetraenoic acid (12-HETE), and of the exocyclic DNA adducts 1,N6-ethenodeoxyadenosine (εdA) and 3,N4-ethenodeoxycytidine (εdC) was investigated in NMRI mouse skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA). In reversible papillomas obtained after 20 weeks of TPA treatment, 15- and 68-fold higher contents of 8-HETE and 12-HETE, respectively, were observed, which were paralleled by 12- and 9-fold increased amounts of εdA and εdC, respectively. When compared to the level in vehicle-treated control skin, these elevations were statistically significant. In irreversible papillomas harvested 20 weeks after the last TPA treatment, the levels of HETEs and etheno−DNA adducts were found to be slightly reduced, as compared to those in reversible papillomas, but were still increased over control levels in age-matched mice. Comparison of mean group values by simple regression analysis showed a close positive correlation between HETE and etheno−DNA adduct levels. Consistent with the miscoding properties of εdA causing mainly A → T transversions, its increased formation in papillomas could thus contribute to this type of mutation in codon 61 of cHa-ras, shown to be a hallmark of DMBA-initiated and TPA-promoted mouse skin carcinogenesis. Although direct evidence that etheno adducts are derived from lipoxygenase-catalyzed metabolites of arachidonic acid is missing, our results implicate DNA damage by oxidative stress and lipid peroxidation as a cause of genetic instability observed at late stages of tumor promotion in mouse skin carcinogenesis. |
DOI: | doi:10.1021/tx000045d |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1021/tx000045d |
| Volltext: https://pubs.acs.org/doi/10.1021/tx000045d |
| DOI: https://doi.org/10.1021/tx000045d |
Datenträger: | Online-Ressource |
Sprache: | eng |
K10plus-PPN: | 1745926577 |
Verknüpfungen: | → Zeitschrift |
Promutagenic etheno−DNA adducts in multistage mouse skin carcinogenesis / Nair, Jagadeesan [VerfasserIn]; July 8, 2000 (Online-Ressource)