Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Apr 18;24(4):532-41.
doi: 10.1021/tx100410y. Epub 2011 Mar 8.

Detection and quantification of specific DNA adducts by liquid chromatography-tandem mass spectrometry in the livers of rats given estragole at the carcinogenic dose

Yuji Ishii  1 , Yuta Suzuki, Daisuke Hibi, Meilan Jin, Kiyoshi Fukuhara, Takashi Umemura, Akiyoshi Nishikawa
Affiliations

Detection and quantification of specific DNA adducts by liquid chromatography-tandem mass spectrometry in the livers of rats given estragole at the carcinogenic dose

Yuji Ishii et al. Chem Res Toxicol. .

Abstract

Estragole (ES) is a natural constituent of several herbs and spices that acts as a carcinogen in the livers of rodents. Given that the proximal electrophilic form of ES with a reactive carbocation is generated by cytochrome P450 and a sulfotransferase metabolizing pathway, there is a possibility that the resultant covalent adducts with DNA bases may play a key role in carcinogenesis. The existence of ES-specific deoxyguanosine (dG) and deoxyadenosine (dA) adducts has already been reported with the precise chemical structures of the dG adducts being confirmed. In the present study, we examined ES-specific dA adduct formation using LC-ESI/MS after the reaction of dA with 1'-acetoxy-ES produced by a sulfotransferase metabolic pathway mimic. Although two peaks were observed in the LC-ESI/MS chromatogram, the identification of ES-3'-N(6)-dA as the measurable peak was determined by NMR analysis. To confirm ES-specific dG and dA adduct formation in vivo, an isotope dilution LC-ESI/MS/MS method applicable to in vivo samples for ES-3'-N(6)-dA together with the two major dG adducts, that is, ES-3'-C8-dG and ES-3'-N(2)-dG, was developed using selected ion recording. The limit of quantification was 0.2 fmol on column for ES-3'-C8-dG and ES-3'-N(2)-dG and 0.06 fmol on column for ES-3'-N(6)-dA, respectively. Using the developing analytical method, we attempted to measure adduct levels in the livers of rats treated with ES at a possible carcinogenic dose (600 mg/kg bw) for 4 weeks. ES-3'-C8-dG, ES-N(2)-dG, and ES-3'-N(6)-dA were detected at levels of 3.5 ± 0.4, 4.8 ± 0.8, and 20.5 ± 1.6/10(6) dG or dA in the livers of ES-treated rats. This quantitative data and newly developed technique for adduct observation in vivo might be helpful for ES hepatocarcinogenesis investigations.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

LinkOut - more resources

-