Creation of a Hyperpermeable Yeast Strain to Genotoxic Agents through Combined Inactivation of PDR and CWP Genes
文献类型：期刊论文
| 作者 | Zhang, Min2; Hanna, Michelle1; Li, Jia1; Butcher, Susan1; Dai, Heping2; Xiao, Wei1 |
| 刊名 | TOXICOLOGICAL SCIENCES
 |
| 出版日期 | 2010-02-01 |
| 卷号 | 113期号:2页码:401-411 |
| 关键词 | Saccharomyces cerevisiae RNR3-lacZ genotoxicity test permeability ABC transporters cell wall |
| ISSN号 | 1096-6080 |
| 通讯作者 | Xiao, W, Univ Saskatchewan, Dept Microbiol & Immunol, 107 Wiggins Rd, Saskatoon, SK S7N 5E5, Canada |
| 中文摘要 | We previously established a genotoxicity detection system based on the transcriptional response of the yeast RNR3 gene to DNA damage. In order to further improve its sensitivity to genotoxicants, we have attempted to increase cell permeability by removing cell wall mannoproteins (CWPs). Here, we report that selected deletion of pleiotropic drug resistance (PDR) genes encoding membrane efflux transporters also enhanced cellular sensitivity to treatment by various genotoxic agents. Furthermore, we have validated our hypothesis that PDR and CWP protect cells through different mechanisms by demonstrating that simultaneous inactivation of the above two pathways resulted in a synergistic enhancement of assay sensitivity as measured by RNR3-lacZ expression and that this effect is at the cell permeability level. The quadruple mutation results in RNR3-lacZ assay sensitivity to tested chemicals that apparently surpasses the industry standard Ames test. We argue that this hyperpermeable yeast mutant strain would be suitable for other chemical-based genotoxic assays. |
| 英文摘要 | We previously established a genotoxicity detection system based on the transcriptional response of the yeast RNR3 gene to DNA damage. In order to further improve its sensitivity to genotoxicants, we have attempted to increase cell permeability by removing cell wall mannoproteins (CWPs). Here, we report that selected deletion of pleiotropic drug resistance (PDR) genes encoding membrane efflux transporters also enhanced cellular sensitivity to treatment by various genotoxic agents. Furthermore, we have validated our hypothesis that PDR and CWP protect cells through different mechanisms by demonstrating that simultaneous inactivation of the above two pathways resulted in a synergistic enhancement of assay sensitivity as measured by RNR3-lacZ expression and that this effect is at the cell permeability level. The quadruple mutation results in RNR3-lacZ assay sensitivity to tested chemicals that apparently surpasses the industry standard Ames test. We argue that this hyperpermeable yeast mutant strain would be suitable for other chemical-based genotoxic assays. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 学科主题 | Toxicology |
| 类目[WOS] | Toxicology |
| 研究领域[WOS] | Toxicology |
| 关键词[WOS] | PROMOTER-REPORTER CONSTRUCT ; SACCHAROMYCES-CEREVISIAE ; MULTIDRUG-RESISTANCE ; DNA-DAMAGE ; PLEIOTROPIC DRUG ; TRANSCRIPTIONAL CONTROL ; ABC TRANSPORTERS ; TESTING SYSTEM ; IN-VIVO ; SENSITIVITY |
| 收录类别 | SCI |
| 资助信息 | Natural Science Foundation of China [30440420603]; Natural Sciences and Engineering Research Council of Canada [138338]; Chinese National Key Laboratory FEBT [2008FB002] |
| 语种 | 英语 |
| WOS记录号 | WOS:000273706200014 |
| 公开日期 | 2010-12-23 |
| 源URL | [http://ir.ihb.ac.cn/handle/342005/13755]  |
| 专题 | 水生生物研究所_水生生物分子与细胞生物学研究中心_期刊论文 |
| 作者单位 | 1.Univ Saskatchewan, Dept Microbiol & Immunol, Saskatoon, SK S7N 5E5, Canada 2.Chinese Acad Sci, Inst Hydrol, Wuhan 430072, Hubei, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Min,Hanna, Michelle,Li, Jia,et al. Creation of a Hyperpermeable Yeast Strain to Genotoxic Agents through Combined Inactivation of PDR and CWP Genes[J]. TOXICOLOGICAL SCIENCES,2010,113(2):401-411. |
| APA | Zhang, Min,Hanna, Michelle,Li, Jia,Butcher, Susan,Dai, Heping,&Xiao, Wei.(2010).Creation of a Hyperpermeable Yeast Strain to Genotoxic Agents through Combined Inactivation of PDR and CWP Genes.TOXICOLOGICAL SCIENCES,113(2),401-411. |
| MLA | Zhang, Min,et al."Creation of a Hyperpermeable Yeast Strain to Genotoxic Agents through Combined Inactivation of PDR and CWP Genes".TOXICOLOGICAL SCIENCES 113.2(2010):401-411. |
入库方式： OAI收割
来源：水生生物研究所
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