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

Archives of Toxicology
Y SuzukiK Ogawa

Abstract

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 pred...Continue Reading

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Citations

Oct 18, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Meilan JinTakasi Umemura
Jun 16, 2014·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Kohei MatsushitaTakashi Umemura
Jan 17, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ludovic Le HégaratValérie Fessard
Nov 28, 2014·Archives of Toxicology·Hermann M Bolt
Oct 30, 2018·Toxicological Research·Takehiko Nohmi
Jun 1, 2013·Journal of Toxicologic Pathology·Kohei MatsushitaTakashi Umemura
Jun 17, 2020·Archives of Toxicology·Andrea HartwigGerhard Eisenbrand
Nov 2, 2014·Environmental and Molecular Mutagenesis·Wei DingMugimane G Manjanatha
Aug 3, 2017·EFSA Journal·UNKNOWN EFSA Scientific CommitteeJan Alexander
Feb 9, 2017·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Takehiko NohmiNaomi Toyoda-Hokaiwado

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