Abstract |
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.
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Authors | Meilan Jin, Aki Kijima, Daisuke Hibi, Yuji Ishii, Shinji Takasu, Kohei Matsushita, Ken Kuroda, Takehiko Nohmi, Akiyoshi Nishikawa, Takasi Umemura |
Journal | Toxicological sciences : an official journal of the Society of Toxicology
(Toxicol Sci)
Vol. 131
Issue 2
Pg. 387-94
(Feb 2013)
ISSN: 1096-0929 [Electronic] United States |
PMID | 23074021
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Mutagens
- methyleugenol
- Eugenol
- Transferases (Other Substituted Phosphate Groups)
- UDP-GlcNAc-undecaprenyl phosphate N-acetylglucosaminyl 1-phosphate transferase
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Topics |
- Animals
- Dose-Response Relationship, Drug
- Eugenol
(analogs & derivatives, toxicity)
- Female
- Immunohistochemistry
- Male
- Mutagenicity Tests
- Mutagens
(toxicity)
- Rats
- Rats, Inbred F344
- Rats, Transgenic
- Transferases (Other Substituted Phosphate Groups)
(genetics)
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