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
リソース情報
ヒト・動物細胞 Hep G2(RCB1886)