論文 - 詳細
| RRC ID | 52283 |
|---|---|
| 著者 | Ono Y, Tomimori N, Hori H, Kitagawa Y, Shibata H. |
| タイトル | Mechanisms of chromosomal aberrations induced by sesamin metabolites in Chinese hamster lung cells. |
| ジャーナル | Mutat Res Genet Toxicol Environ Mutagen |
| Abstract |
Sesamin is a major lignan in sesame seeds and oil. We previously demonstrated that sesamin induces chromosomal aberrations (CA) in Chinese hamster lung (CHL/IU) cells in the presence of a metabolic activation system (S9 mix), although no genotoxicity was detected in vivo. To clarify the mechanism of CA induction by sesamin, we identified its principal active metabolite. A mono-catechol derivative, [2-(3,4-methylenedioxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabi-cyclo[3.3.0]octane (SC-1)], was previously identified in culture medium when sesamin was incubated with S9 mix. In the present study, we show that SC-1 induces CA in CHL/IU cells but not in human hepatoblastoma (HepG2) cells. SC-1 was unstable in culture medium. Addition of glutathione (GSH) to the incubation mixture decreased the rate of decomposition and also suppressed induction of CA in CHL/IU cells. These results indicate that SC-1 itself may not contribute to the induction of CA. Two GSH adducts of SC-1 were identified when SC-1 was incubated with GSH, suggesting that SC-1 was converted to the semiquinone/quinone form and then conjugated with GSH in the culture medium. Sodium sulfite (a quinone-responsive compound) also suppressed CA induction by SC-1. These findings strongly suggest that SC-1 is oxidized to semiquinone/quinone derivatives extracellularly in culture medium, that these derivatives are responsible for the induction of CA in CHL/IU cells, and therefore that the positive results obtained with sesamin in in vitro CA tests using CHL/IU cells may not be relevant to the assessment of in vivo activity. |
| 巻・号 | 822 |
| ページ | 19-26 |
| 公開日 | 2017-10-1 |
| DOI | 10.1016/j.mrgentox.2017.06.006 |
| PII | S1383-5718(17)30038-4 |
| PMID | 28844238 |
| MeSH | Animals Bridged Bicyclo Compounds, Heterocyclic / metabolism Bridged Bicyclo Compounds, Heterocyclic / toxicity* Cell Culture Techniques Chromosome Aberrations / chemically induced* Cricetinae Cyclooctanes / metabolism Cyclooctanes / toxicity* Dioxoles / metabolism Dioxoles / toxicity* Dose-Response Relationship, Drug Glutathione / metabolism Hep G2 Cells Humans Lignans / metabolism Lignans / toxicity* Liver / metabolism Liver Extracts Lung / cytology Lung / drug effects |
| IF | 2.463 |
| 引用数 | 0 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2(RCB1886) |