Methods and diagnostic kits for determining toxicity utilizing E

Tent – canopy – umbrella – or cane – Umbrella – Self-opening and closing

Patent

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

435 29, 43525233, C12Q 168, C12Q 102, C12N 121

Patent

active

055852327

ABSTRACT:
This invention provides methods and diagnostic kits for determining the toxicity of a compound. The methods and diagnostic kits of this invention employ a plurality of E. coli hosts, each of which have been transformed with a DNA sequence encoding a unique stress promoter fused to a gene which encodes an assayable product. Each of these stress promoters is induced by exposure to a different type of cellular stress. The stress promoters utilized in this invention, in toto, comprises those which respond to redoxo stress, DNA stress, protein stress, energy stress and pH stress. The methods and diagnostic kits of this invention may be employed to characterize and quantify the toxicity of a compound, as well as to identify the cellular mechanism of its toxic action. The methods disclosed herein represent a more humane and economical alternative to the live animal testing currently employed to test the toxicity of new chemicals. Moreover, the methods of this invention, yield information concerning the action of a compound on a subcellular level. This information may be utilized to design antitoxins to compounds found to be toxic and in active drug design.

REFERENCES:
patent: 4849335 (1989-07-01), Hofnung et al.
Maki, Nature 355:273-275 (1992).
Saporito, J. Bacteriol. 170(11):5141-5142(1988).
Cowing, Proc. Natl. Acad. Sci USA 82: 2679-2685 (1985).
Chin, J. Biol. Chem. 265(24): 11718-11728 (1988).
Kitagawa, J. Bacterol., 173(14): 4247-4253 (1991).
Ross, J. Bacteriol. 171: 4009-4018 (1989).
Brickman, J. Mol. Biol. 212 : 669-682 (1990).
Neidhardt, E. coli and S. typhimurium, ASM Press, pp. 170-1200 (1989).
Ner, Biochemistry 22: 5243-5248 (1983).
Iuchi, J. Bacteriol, 172(10):6020-6025 (1990).
Minagawa, J. Biol. Chem. 265:11198-11203 (1990).
von Meyenburg, EMBO J., 9(a): 2357-2363 (1985).
Kanazawa, Biochem. Biophys. Res. Comm. 103:604-612 (1981).
Silverman, J. Bacteriol. 120(3):1196-1203 (1974).
Kuwajima, J. Bacterol.:168 :1479-1483 (1987).
Triggs-Raine, Gene:52:121-128 (1987).
Touati, J. Bacteriol., 170: 2511-2520 (1988).
Loewen, J. Bacteriol. 162(2): 661-667 (1985).
Storz, J. Bacteriol. 171(4):2049-2055 (1989).
Gushima, Nucl. Acids. Res. 12(24):9299-9307 (1984).
Demple, Bioassays 6: 157-160 (1987).
Lilley, Mol. Microbiol. 5(4):779-783 (1991).
Drlica, Biochemistry: 27(7):2253-2259 (1988).
Tse-Dinh, J Mol. Biol. 202: 735-742 (1988).
H. M. Hassan et al., "Regulatory Roles of Fnr, Fur, and Arc in Expression of Manganese-containing Superoxide Dismutase in Escherichia coli", Proc. Natl. Acad. Sci. USA, 89, pp. 3217-3221 (Apr. 1992).
Z. Aliabadi et al., "Novel Regulatory Loci Controlling Oxygen-and pH-Regulated Gene Expression in Salmonella Typhimurium", J. Bacteriol., 170, pp. 842-851 (1988).
A. Barron et al., "Regulation of Envelope Protein Composition During Adaptation to Osmotic Stress in Escherichia coli", J. Bacteriol., 167, pp. 433-438 (1986).
T. J. Brickman et al., "Regulation of Divergent Transcription from the Iron-Responsive fepB-entC Promoter-Operator Regions in Escherichia coli", J. Mol. Biol., 212, pp. 669-682 (1990).
A. Carlioz et al., "Isolation of Superoxide Dismutase in Escherichia coli: Is Superoxide Dismutase Necessary for Aerobic Life?", EMBO J., 5, pp. 623-630 (1986).
S. Caseragola et al., "Quantitative Evaluation of recA Expression in Escherichia coli", Mol. Gen. Genet., 185, pp. 430-439 (1982).
D. T. Chin et al., "Sequence of the lon Gene in Escherichia coli", J. Biol. Chem., 263, pp. 11718-11728 (1988).
D. W. Cowing et al., "Consensus Sequence for Escherichia coli Heat Shock Gene Promoters", Proc. Natl. Acad. Sci. USA, 82, pp. 2679-2683 (1985).
R. P. Cunningham et al., "Endonuclease III (nth) Mutants of Escherichia coli", Proc. Natl. Acad. Sci. USA, 82, pp. 474-478 (1985).
S. B. Farr et al., "Oxidative Stress Responses in Escherichia coli and Salmonella typhimurium", Microbiol. Rev., 55, pp. 561-585. (1991).
R. J. Fram et al., "Gene Expression Caused by Alkylating Agents and cis-Diamminedichloroplatinum(II) in Escherichia coli", Cancer Res., 48, pp. 4823-4826 (1988).
J. T. Greenburg et al., "Positive Control of a Global Antioxidant Defense Regulon Activated by Superoxide-Generating Agents in Escherichia coli", Proc. Natl. Acad. Sci. USA, 87, pp. 6181-6185 (1990).
J. T. Greenburg et al., "Activation of Oxidative Stress Genes by Mutations the at, soxQ/cfxB/marA Locus of Escherichia coli", J. Bacteriol., 173, pp. 4433-4439 (1991).
S. Iuchi et al., "Requirement for Terminal Cytochromes in Generation of the Aerobic Signal for the arc Regulatory System in Escherichia coli: Study Utilizing Deletions and lac Fusions of cyo and cyd",. J. Bacteriol., 172, pp. 6020-6025 (1990).
G. T. Javor et al., "Thiol-Senstive Promoters of Escherichia coli", J. Bacteriol., 170, pp. 3291-3295 (1988).
C. J. Kenyon et al., "Regulation of Damage-Inducible Genes in Escherichia coli", J. Mol. Biol., 160, pp. 445-457 (1982).
C. J. Kenyon et al., "Expression of the E. coli uvrA Gene is Inducible", Nature, 289, pp. 808-812 (1981).
M. Kitigawa et al., "Expression of ClpB, and Analog of the ATP-Dependent Protease Regulatory Subunit in Escherichia coli, Is Controlled by a Heat Shock .sigma. Factor (.sigma..sup.32 )", J. Bacteriol., 173, 4247-4253 (1991).
J.-M. Lacroix et al., "The modA Locus of Escherichia coli Consists of an Operon Under Osmotic Control", Molec. Microbiol., 5, pp. 1745-1753 (1991).
R. Lange et al., "Identification of a Central Regulator of Stationary-Phase Gene Expression in Escherichia coli", Mol. Microbiol., 5, pp. 49-59 (1991).
J. Minagawa et al., "Transcriptional Regulation of the Cytochrome b.sub.562 -o Complex in Escherichia coli", J. Biol. Chem., 265, pp. 11198-11203 (1990).
Y. Nakabeppu et al., "Purification and Structure of the Intact Ada Regulatory Protein of Escherichia coli K12, O.sup.6 -Methylguanine-DNA Methyltransferase", J. Biol. Chem., 260, pp. 7281-7288 (1985).
T. Ohta et al., "The SOS-Function-Inducing Activity of Chemical Mutagens in Escherichia coli", Mutation Research, 131, pp. 101-109 (1984).
P. Quillardet et al., "Induction of the SOS Function sfiA in E. coli Strains Deficient or Proficient in Excision Repair", J. Bacteriol., 157, pp. 36-38 (1984).
W. Ross et al., "Genetic Analysis of Transcriptional Activation and Repression in the Tn21 mer Operon", J. Bacteriol., 171, pp. 4009-4018 (1988).
S. Spiro et al., "Adaptive Responses to Oxygen Limitation in Escherichia coli", TIBS, 16, pp. 310-313 (1991).
K. Tao et al., "Purification and Characterization of the Escherichia coli OxyR Protein, the Positive Regulator for a Hydrogen Peroxide-Inducible Regulon", J. Biochem., 109, pp. 262-266 (1991).
B. Tardat et al., "Two Global Regulators Repress the Anaerobic Expression of MnSOD in Escherichia coli: : Fur (Ferric Uptake Regulation) and Arc (Aerobic Respiration Control)", Mol. Microbiol., 5, pp. 455-465 (1991).
A. Tartaglia et al., "Identification and Molecular Analysis of oxyR-Regulated Promoters Important for the Bacterial Adaptation to Oxidative Stress", J. Mol. Biol., 210, pp. 709-719 (1989).
I. R. Tsaneva et al., "soxR, a Locus Governing a Superoxide Response Regulon in Escherichia coli K-12", J. Bacteriol., 172, pp. 4197-4205 (1990).
Y.-C. Tse-Dinh et al., "Complete Nucleotide Sequence of the topA Gene Encoding Escherichia coli DNA Topoisomerase I", J. Mol. Biol., 191, pp. 321-331 (1986).
Y.-C. Tse-Dinh et al., "Multiple Promoters for Transcription of the Escherichia coli DNA Topoisomerase I Gene and Their Regulation by DNA Supercoiling", J. Mol. Biol., 202, pp. 735-742 (1988).
Kogoma et al. P.N.A.S. 85:4799-4803, 1988.
McCann et al. P.N.A.S. 72:5135-5139 1975.
Keyse et al. P.N.A.S. 86:99-103, 1989.

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Methods and diagnostic kits for determining toxicity utilizing E does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Methods and diagnostic kits for determining toxicity utilizing E, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods and diagnostic kits for determining toxicity utilizing E will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-1990337

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.