HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

In vivo genotoxicity of methyleugenol in gpt delta transgenic rats following medium-term exposure.

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.
AuthorsMeilan Jin, Aki Kijima, Daisuke Hibi, Yuji Ishii, Shinji Takasu, Kohei Matsushita, Ken Kuroda, Takehiko Nohmi, Akiyoshi Nishikawa, Takasi Umemura
JournalToxicological 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
PMID23074021 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Mutagens
  • methyleugenol
  • Eugenol
  • Transferases (Other Substituted Phosphate Groups)
  • UDP-GlcNAc-undecaprenyl phosphate N-acetylglucosaminyl 1-phosphate transferase
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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: