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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 PublicationTOXICOLOGICAL SCIENCES
ISSN1096-6080
Volume103Issue:1Pages:68-76
AbstractWe 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.
SubtypeArticle
KeywordRnr3-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 AreaToxicology
DOI10.1093/toxsci/kfn034
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Language英语
WOS Research AreaToxicology
WOS SubjectToxicology
WOS IDWOS:000254955500008
WOS KeywordPLEIOTROPIC DRUG-RESISTANCE ; SACCHAROMYCES-CEREVISIAE ; MULTIDRUG-RESISTANCE ; CALCOFLUOR WHITE ; TESTING SYSTEM ; WALL POROSITY ; CONGO RED ; MEMBRANE ; MANNOPROTEINS ; SENSITIVITY
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Cited Times:26[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/152342/8160
Collection期刊论文
Corresponding AuthorDai, HP, Chinese Acad Sci, Inst Hydrol, 7 Donghu Rd S, Wuhan 430072, Peoples R China
Affiliation1.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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