Journal Article

<i>In Vivo</i> Genotoxicity of Methyleugenol in <i>gpt</i> Delta Transgenic Rats Following Medium-Term Exposure

Meilan Jin, Aki Kijima, Daisuke Hibi, Yuji Ishii, Shinji Takasu, Kohei Matsushita, Ken Kuroda, Takehiko Nohmi, Akiyoshi Nishikawa and Takasi Umemura

in Toxicological Sciences

Volume 131, issue 2, pages 387-394
Published in print February 2013 | ISSN: 1096-6080
Published online October 2012 | e-ISSN: 1096-0929 | DOI:
In Vivo Genotoxicity of Methyleugenol in gpt Delta Transgenic Rats Following Medium-Term Exposure

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Methyleugenol (MEG), which is commonly used as a fragrance and flavoring agent, has been shown to induce hepatocellular tumors in rodents. However, the role of genotoxicity as a possible mechanism of action is not fully understood even though the DNA-reactive metabolite of MEG has been identified. In this study, a gpt delta transgenic rat model was used to clarify whether genotoxic mechanisms are involved in MEG-induced hepatocarcinogenesis following medium-term exposure. F344 gpt delta rats were subjected to repeated oral administration of MEG at dosages of 0, 10, 30, or 100mg/kg (a carcinogenic dose) for 13 weeks. The relative weight of the liver of the male and female rats that were administered 100mg/kg MEG and the absolute weight of the liver of the male rats that were administered 100mg/kg MEG were significantly increased. In addition, the number and area of glutathione S-transferase placental form (GST-P) positive foci and proliferating cell nuclear antigen (PCNA) positive cell ratios in the hepatocytes were significantly increased in the male and female rats that were administered 100mg/kg MEG compared with the control animals. In the in vivo mutation assays, a significant increase in the gpt and Spi mutant frequencies was observed in both sexes at the carcinogenic dose. These results suggest the possible participation of genotoxic mechanisms in MEG-induced hepatocarcinogenesis.

Keywords: methyleugenol; in vivo genotoxicity; gpt delta rats

Journal Article.  4595 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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