Deletion of yeast CWP genes enhances cell permeability to genotoxic agents | |
Zhang, Min1; Liang, Yuping2; Zhang, Xiaohua1; Xu, Ying1; Dai, Heping1; Xiao, Wei1,2; Dai, HP, Chinese Acad Sci, Inst Hydrol, 7 Donghu Rd S, Wuhan 430072, Peoples R China | |
2008-05-01 | |
Source Publication | TOXICOLOGICAL SCIENCES
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ISSN | 1096-6080 |
Volume | 103Issue:1Pages:68-76 |
Abstract | We have previously reported the development of a novel genotoxic testing system based on the transcriptional response of the yeast RNR3-lacZ reporter gene to DNA damage. This system appears to be more sensitive than other similar tests in microorganisms, and is comparable with the Ames test. In an effort to further enhance detection sensitivity, we examined the effects of altering major cell wall components on cell permeability and subsequent RNR3-lacZ sensitivity to genotoxic agents. Although inactivation of single CWP genes encoding cell wall mannoproteins had little effect, the simultaneous inactivation of both CWP1 and CWP2 had profound effects on the cell wall structure and permeability. Consequently, the RNR3-lacZ detection sensitivity is markedly enhanced, especially to high molecular weight compounds such as 4-nitroquinoline-N-oxide (> sevenfold) and phleomycin (> 13-fold). In contrast, deletion of genes encoding representative membrane components or membrane transporters had minor effects on cell permeability. We conclude that the yeast cell wall mannoproteins constitute the major barrier to environmental genotoxic agents and that their removal will significantly enhance the sensitivity of RNR-lacZ as well as other yeast-based genotoxic tests.; We have previously reported the development of a novel genotoxic testing system based on the transcriptional response of the yeast RNR3-lacZ reporter gene to DNA damage. This system appears to be more sensitive than other similar tests in microorganisms, and is comparable with the Ames test. In an effort to further enhance detection sensitivity, we examined the effects of altering major cell wall components on cell permeability and subsequent RNR3-lacZ sensitivity to genotoxic agents. Although inactivation of single CWP genes encoding cell wall mannoproteins had little effect, the simultaneous inactivation of both CWP1 and CWP2 had profound effects on the cell wall structure and permeability. Consequently, the RNR3-lacZ detection sensitivity is markedly enhanced, especially to high molecular weight compounds such as 4-nitroquinoline-N-oxide (> sevenfold) and phleomycin (> 13-fold). In contrast, deletion of genes encoding representative membrane components or membrane transporters had minor effects on cell permeability. We conclude that the yeast cell wall mannoproteins constitute the major barrier to environmental genotoxic agents and that their removal will significantly enhance the sensitivity of RNR-lacZ as well as other yeast-based genotoxic tests. |
Subtype | Article |
Keyword | Rnr3-lacz Yeast Cell Wall Mannoprotein Genotoxicity Test Sensitivity Permeability |
Department | [Zhang, Min; Zhang, Xiaohua; Xu, Ying; Dai, Heping; Xiao, Wei] Chinese Acad Sci, Inst Hydrol, Wuhan 430072, Peoples R China; [Liang, Yuping; Xiao, Wei] Univ Saskatchewan, Dept Microbiol & Immunol, Saskatoon, SK S7N 5E5, Canada |
Subject Area | Toxicology |
DOI | 10.1093/toxsci/kfn034 |
WOS Headings | Science & Technology ; Life Sciences & Biomedicine |
Indexed By | SCI |
Language | 英语 |
WOS Research Area | Toxicology |
WOS Subject | Toxicology |
WOS ID | WOS:000254955500008 |
WOS Keyword | PLEIOTROPIC DRUG-RESISTANCE ; SACCHAROMYCES-CEREVISIAE ; MULTIDRUG-RESISTANCE ; CALCOFLUOR WHITE ; TESTING SYSTEM ; WALL POROSITY ; CONGO RED ; MEMBRANE ; MANNOPROTEINS ; SENSITIVITY |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://ir.ihb.ac.cn/handle/152342/8160 |
Collection | 期刊论文 |
Corresponding Author | Dai, HP, Chinese Acad Sci, Inst Hydrol, 7 Donghu Rd S, Wuhan 430072, Peoples R China |
Affiliation | 1.Chinese Acad Sci, Inst Hydrol, Wuhan 430072, Peoples R China 2.Univ Saskatchewan, Dept Microbiol & Immunol, Saskatoon, SK S7N 5E5, Canada |
Recommended Citation GB/T 7714 | Zhang, Min,Liang, Yuping,Zhang, Xiaohua,et al. Deletion of yeast CWP genes enhances cell permeability to genotoxic agents[J]. TOXICOLOGICAL SCIENCES,2008,103(1):68-76. |
APA | Zhang, Min.,Liang, Yuping.,Zhang, Xiaohua.,Xu, Ying.,Dai, Heping.,...&Dai, HP, Chinese Acad Sci, Inst Hydrol, 7 Donghu Rd S, Wuhan 430072, Peoples R China.(2008).Deletion of yeast CWP genes enhances cell permeability to genotoxic agents.TOXICOLOGICAL SCIENCES,103(1),68-76. |
MLA | Zhang, Min,et al."Deletion of yeast CWP genes enhances cell permeability to genotoxic agents".TOXICOLOGICAL SCIENCES 103.1(2008):68-76. |
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