In vivo genotoxicity of methyleugenol in gpt delta transgenic rats following medium-term exposure.
Toxicol Sci
; 131(2): 387-94, 2013 Feb.
Article
em En
| MEDLINE
| ID: mdl-23074021
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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Base de dados:
MEDLINE
Assunto principal:
Eugenol
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Transferases (Outros Grupos de Fosfato Substituídos)
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Mutagênicos
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article