新科学想法 › 文献管理 › 浏览文献

Murine hepatoma (Hepa1c1c7) cells: A responsive in vitro system for chemoprotective enzyme induction by organoselenium compounds

jgsun 添加于 2010-10-21 22:06 | 2244 次阅读 | 0 个评论

作者
ELSAYED W, ABOULFADL T, ROBERTS J, LAMB J, FRANKLIN M
摘要
Murine (Hepa1c1c7) hepatoma cells are a suitable in vitro system for investigating the regulation of chemoprotective enzymes by selenazolidines, novel l -selenocysteine prodrugs developed as potential chemopreventive agents. They are less sensitive to the cytotoxic effects of both selenite and the less toxic selenazolidines than rat hepatoma (H4IIE) cells. All four selenazolidine 4-carboxylic acid (SCA) derivatives examined elevated thioredoxin reductase (Txnrd1), alpha-class glutathione transferases (Gsta), and UDP-glucuronosyltransferase (Ugt)1a6 mRNAs. NAD(P)H-quinone oxidoreductase (Nqo1) was induced by the three 2-alkyl derivatives (2-cyclohexylSCA, 2-butylSCA, and 2-methylSCA) but not SCA itself. Transcripts of mu- and pi-class glutathione transferases were induced only by 2-cyclohexylSCA and 2-butylSCA. Only Gsta and Txnrd1 transcripts were elevated by l -selenomethionine, l -selenocystine, or Se-methyl- l -selenocysteine. Txnrd1, Gsta, Nqo1, and Gstp responses to selenazolidines were all abolished by actinomycin D while Ugt1a6 responses were not. Induction responses to the selenazolidines were also eliminated (most) or reduced (Txnrd1 by 2-methylSCA) by cycloheximide, with the exception of Ugt1a6. The Ugt1a6 mRNA levels in the presence of SCAs and cycloheximide were similar to those with cycloheximide alone, and were almost double those of vehicle-treated cells. Thus, Hepa1c1c7 cells appear to provide a viable platform for the study of protective enzyme regulation by selenocompounds, and with the exception of Ugt1a6, the mRNA elevations from selenazolidines are transcriptionally dependent.
详细资料
- 文献种类:期刊
- 期刊名称: Toxicology in Vitro
- 期刊缩写: Toxicology in Vitro
- 期卷页: 2007年第21卷第1期 157-164页
- ISBN: 0887-2333
相关链接 DOI URL