WO2000047761A3 - High-throughput toxicological testing using cultured organisms and cells - Google Patents

High-throughput toxicological testing using cultured organisms and cells Download PDF

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Publication number
WO2000047761A3
WO2000047761A3 PCT/US2000/003557 US0003557W WO0047761A3 WO 2000047761 A3 WO2000047761 A3 WO 2000047761A3 US 0003557 W US0003557 W US 0003557W WO 0047761 A3 WO0047761 A3 WO 0047761A3
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WO
WIPO (PCT)
Prior art keywords
assay
damage
ability
mutant
testing
Prior art date
Application number
PCT/US2000/003557
Other languages
French (fr)
Other versions
WO2000047761A2 (en
Inventor
Spencer B Farr
Bryan A Shiloff
Original Assignee
Phase 1 Molecular Toxicology I
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Phase 1 Molecular Toxicology I filed Critical Phase 1 Molecular Toxicology I
Priority to EP00908601A priority Critical patent/EP1153137A2/en
Publication of WO2000047761A2 publication Critical patent/WO2000047761A2/en
Publication of WO2000047761A3 publication Critical patent/WO2000047761A3/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
    • C12Q1/025—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5014—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing toxicity

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Toxicology (AREA)
  • Biomedical Technology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Microbiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Urology & Nephrology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Biophysics (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Food Science & Technology (AREA)

Abstract

Methods and kits for measuring mutant hypersensitivity assay using high-throughput screening methodology to evaluate the mechanisms of toxicity of chemicals. The assay is performed in multi-well plates, such as those having 96 wells, making the process conducive to testing many compounds in a short period of time. The assay is versatile in that it can test compounds for ability to cause, for example, DNA damage, ability to mutate genetic material (mutagenicity), the ability to cause cancer (carcenogenicity), cause protein or membrane damage, energy depletion, mitochondrial damage, as well as the more general genotoxicity. Thus, the term toxicity, as used in this disclosure, is intended to encompass all of these types of effects. Furthermore, the assay can detect oxidative stress, protein damage, cell cycle disruption, energy charge and depletion, microtubule disruption or onset of metabolic competency through overexpression of human gene inserts encoding metabolism genes or incorporation of S9 fraction. In a preferred embodiment of the present invention, wildtype (wt) yeast and respective mutants are dosed with the desired chemical and yeast growth is determined using turbidimetry. Dose response curves are generated and mutant sensitivity to the compound relative to its parent (relative sensitivity) calculated. Relative sensitivities which are statistically significant indicate a hypersensitivity of the mutant to the test compound. The assay therefore provides an inexpensive, reliable, short term toxicity test which is an excellent alternative to animal testing and which provides valuable information about the mechanism of action of a compound. The present invention has applications to the pharmaceutical industry, environmental testing and clinical studies.
PCT/US2000/003557 1999-02-12 2000-02-11 High-throughput toxicological testing using cultured organisms and cells WO2000047761A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP00908601A EP1153137A2 (en) 1999-02-12 2000-02-11 High-throughput toxicological testing using cultured organisms and cells

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US24971999A 1999-02-12 1999-02-12
US09/249,719 1999-02-12

Publications (2)

Publication Number Publication Date
WO2000047761A2 WO2000047761A2 (en) 2000-08-17
WO2000047761A3 true WO2000047761A3 (en) 2000-11-30

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/003557 WO2000047761A2 (en) 1999-02-12 2000-02-11 High-throughput toxicological testing using cultured organisms and cells

Country Status (2)

Country Link
EP (1) EP1153137A2 (en)
WO (1) WO2000047761A2 (en)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU7986000A (en) * 1999-09-24 2001-04-24 Johns Hopkins University, The Colorimetric test for agents that induce mitrochondrial dysfunction
WO2002008453A2 (en) 2000-07-21 2002-01-31 Phase-1 Molecular Toxicology Canine toxicity genes
US7415358B2 (en) 2001-05-22 2008-08-19 Ocimum Biosolutions, Inc. Molecular toxicology modeling
US7447594B2 (en) 2001-07-10 2008-11-04 Ocimum Biosolutions, Inc. Molecular cardiotoxicology modeling
US7469185B2 (en) 2002-02-04 2008-12-23 Ocimum Biosolutions, Inc. Primary rat hepatocyte toxicity modeling
AU2003237677A1 (en) * 2002-05-23 2003-12-12 Tenaxis Gmbh Screening for compounds having an effect on cells using microtiter plates
GB0215509D0 (en) * 2002-07-04 2002-08-14 Novartis Ag Marker genes
GB0921712D0 (en) 2009-12-11 2010-01-27 Ge Healthcare Uk Ltd Methods of detecting DNA damage
CN109061141A (en) * 2018-06-15 2018-12-21 光景生物科技(苏州)有限公司 A kind of turbid detection method of latex enhancing immune transmittance
CN111418383B (en) * 2020-04-16 2021-08-24 桂林理工大学 Screening method of chemical regulating agent under pollution exposure based on root development parameters
AU2022451480A1 (en) 2022-03-30 2024-10-17 Infinite D.O.O. A method for predictive testing of agents to assess triggering and suppressing adverse outcomes and/or diseases
CN117778417B (en) * 2023-12-08 2024-10-15 山东省农业科学院 ScHSP78 gene for regulating and controlling microbial mercury resistance and mercury accumulation and application thereof

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0063522A2 (en) * 1981-04-14 1982-10-27 Institut Pasteur An inducible DNA replication-cell division coupling mechanism in Escherichia coli
WO1992014817A1 (en) * 1991-02-16 1992-09-03 Imperial Cancer Research Technology Limited In vivo assay systems for metabolic routes
DE4317595A1 (en) * 1993-05-24 1994-12-01 Fzb Biotechnik Gmbh Method for determining the toxicity of samples by bioassay
JPH07143890A (en) * 1993-05-28 1995-06-06 Toyobo Co Ltd Rad51 structure gene

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0063522A2 (en) * 1981-04-14 1982-10-27 Institut Pasteur An inducible DNA replication-cell division coupling mechanism in Escherichia coli
WO1992014817A1 (en) * 1991-02-16 1992-09-03 Imperial Cancer Research Technology Limited In vivo assay systems for metabolic routes
DE4317595A1 (en) * 1993-05-24 1994-12-01 Fzb Biotechnik Gmbh Method for determining the toxicity of samples by bioassay
JPH07143890A (en) * 1993-05-28 1995-06-06 Toyobo Co Ltd Rad51 structure gene

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, vol. 128, no. 14, 6 April 1998, Columbus, Ohio, US; abstract no. 163843c, HAUSER B ET AL: "Dependence of genotoxicity of benzo [a]-pyrene suspensions in Mutatox test on dissolved concentration and S9 addition" page 182; column l; XP002901035 *
DATABASE WPI Section Ch Week 199531, Derwent World Patents Index; Class B04, AN 1995-236467, XP002901036 *
ECOTOXICOL. ENVIRON. SAF., vol. 38, no. 3, 1997, pages 224 - 226 *
SCHLEGEL H G: "Allgemeine Mikrobiologie", 1985, GEORG THIEME VERLAG, 6TH EDITION, STUTTGART, DE, XP002901034 *

Also Published As

Publication number Publication date
WO2000047761A2 (en) 2000-08-17
EP1153137A2 (en) 2001-11-14

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