Possible involvement of genotoxic mechanisms in estragole-induced hepatocarcinogenesis in rats

DOI PDF Web Site Web Site PubMed 被引用文献11件 参考文献23件

書誌事項

公開日
2012-05-11
資源種別
journal article
権利情報
  • http://www.springer.com/tdm
DOI
  • 10.1007/s00204-012-0865-8
公開者
Springer Science and Business Media LLC

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説明

Estragole (ES) is a natural organic compound used frequently as a flavoring food additive. Although it has been reported to be tumorigenic and induce DNA adducts in the mouse liver, there have been no reports regarding ES hepatocarcinogenicity in rats. In the current study, we therefore examined potent carcinogenicity, DNA adduct formation and in vivo genotoxicity of ES in the livers of wild and reporter gene-carrying F344 rats. Males were administered 600 mg/kg bw ES by gavage and sequentially sacrificed at weeks 4, 8 and 16 for GST-P and PCNA immunohistochemistry and measurement of ES-specific DNA adducts by LC-MS/MS in the livers. GST-P-positive foci increased with time in ES-treated rats from week 4, PCNA-labeling indices being similarly elevated at both weeks 4 and 8. ES-specific DNA adducts such as ES-3'-N(2)-dG, 3'-8-dG and 3'-N(6)-dA were consistently detected, particularly at week 4. In a second study, male F344 gpt delta rats were administered 0, 22, 66, 200 or 600 mg/kg bw ES for 4 weeks. Gpt mutant frequency in the liver was increased in a dose-dependent manner, with significance at 200 and 600 mg/kg bw in good correlation with PCNA-labeling indices. Mutation spectra analysis showed A:T to G:C transitions to be predominantly increased in line with the formation of ES-3'-N(6)-dA or 3'-8-dG. These results indicate that ES could be a possible genotoxic hepatocarcinogen in the rat, at least when given at high doses.

収録刊行物

  • Archives of Toxicology

    Archives of Toxicology 86 (10), 1593-1601, 2012-05-11

    Springer Science and Business Media LLC

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