Gene expression changes associated with cytotoxicity identified using cDNA arrays.

Article Details

Citation

Gore MA, Morshedi MM, Reidhaar-Olson JF

Gene expression changes associated with cytotoxicity identified using cDNA arrays.

Funct Integr Genomics. 2000 Sep;1(2):114-26.

PubMed ID
11793227 [ View in PubMed
]
Abstract

In order to investigate gene expression changes associated with cytotoxicity, we used cDNA arrays to monitor the expression of over 5,000 genes in response to toxic stress in the HepG2 liver cell line. Cells were treated with cytotoxic doses of acetaminophen, caffeine or thioacetamide for nine time points ranging from 1 to 24 h. Samples of mRNA from each time point were used to prepare radiolabeled cDNA, which was hybridized to nylon-membrane-based cDNA arrays. High-stringency washes were applied to reduce cross-hybridization. Analysis of spot intensities revealed that each compound led to approximately 150-250 gene expression changes that were sustained over at least three adjacent time points. The affected genes could be classified into clusters based on their temporal patterns of differential expression. A common set of 44 genes showed similar expression changes in response to all three compounds. Of these changes, 90% could be confirmed by quantitative RT-PCR analysis. The results indicate that detailed array-based time-course studies, coupled with a sensitive and highly specific confirmation assay, provide a powerful means of identifying cytotoxicity-associated gene expression changes.

DrugBank Data that Cites this Article

Pharmaco-transcriptomics
DrugDrug GroupsGeneGene IDChangeInteractionChromosome
AcetaminophenApprovedACAT239
downregulated
Acetaminophen results in decreased expression of ACAT2 mRNA6q25.3
AcetaminophenApprovedACIN122985
upregulated
Acetaminophen results in increased expression of ACIN1 mRNA14q11.2
AcetaminophenApprovedACSL32181
upregulated
Acetaminophen results in increased expression of ACSL3 mRNA2q36.1
AcetaminophenApprovedALDH18A15832
downregulated
Acetaminophen results in decreased expression of ALDH18A1 mRNA10q24.1
AcetaminophenApprovedANG283
downregulated
Acetaminophen results in decreased expression of ANG mRNA14q11.2
AcetaminophenApprovedARL6IP123204
upregulated
Acetaminophen results in increased expression of ARL6IP1 mRNA16p12.3
AcetaminophenApprovedATP5J29551
downregulated
Acetaminophen results in decreased expression of ATP5J2 mRNA7q22.1
AcetaminophenApprovedCALU813
downregulated
Acetaminophen results in decreased expression of CALU mRNA7q32.1
AcetaminophenApprovedCDK41019
downregulated
Acetaminophen results in decreased expression of CDK4 mRNA12q14.1
AcetaminophenApprovedCYC11537
downregulated
Acetaminophen results in decreased expression of CYC1 mRNA8q24.3
AcetaminophenApprovedDAD11603
downregulated
Acetaminophen results in decreased expression of DAD1 mRNA14q11.2
AcetaminophenApprovedEIF110209
upregulated
Acetaminophen results in increased expression of EIF1 mRNA17q21.2
AcetaminophenApprovedGLRX2745
downregulated
Acetaminophen results in decreased expression of GLRX mRNA5q15
AcetaminophenApprovedGLT8D155830
downregulated
Acetaminophen results in decreased expression of GLT8D1 mRNA3p21.1
AcetaminophenApprovedGLUD12746
downregulated
Acetaminophen results in decreased expression of GLUD1 mRNA10q23.2
AcetaminophenApprovedGSTO19446
downregulated
Acetaminophen results in decreased expression of GSTO1 mRNA10q25.1
AcetaminophenApprovedIGFBP13484
upregulated
Acetaminophen results in increased expression of IGFBP1 mRNA7p12.3
AcetaminophenApprovedLDHA3939
downregulated
Acetaminophen results in decreased expression of LDHA mRNA11p15.1
AcetaminophenApprovedMGST14257
downregulated
Acetaminophen results in decreased expression of MGST1 mRNA12p12.3
AcetaminophenApprovedMT1B4490
upregulated
Acetaminophen results in increased expression of MT1B mRNA16q13
AcetaminophenApprovedMT1G4495
upregulated
Acetaminophen results in increased expression of MT1G mRNA16q13
AcetaminophenApprovedMT1H4496
upregulated
Acetaminophen results in increased expression of MT1H mRNA16q13
AcetaminophenApprovedOAT4942
upregulated
Acetaminophen results in increased expression of OAT mRNA10q26.13
AcetaminophenApprovedPRELID127166
downregulated
Acetaminophen results in decreased expression of PRELID1 mRNA5q35.3
AcetaminophenApprovedPSME310197
downregulated
Acetaminophen results in decreased expression of PSME3 mRNA17q21.31
AcetaminophenApprovedRPS6KA36197
downregulated
Acetaminophen results in decreased expression of RPS6KA3 mRNAXp22.12
AcetaminophenApprovedRRS123212
upregulated
Acetaminophen results in increased expression of RRS1 mRNA8q13.1
AcetaminophenApprovedSCFD123256
downregulated
Acetaminophen results in decreased expression of SCFD1 mRNA14q12
AcetaminophenApprovedSEC136396
downregulated
Acetaminophen results in decreased expression of SEC13 mRNA3p25.3
AcetaminophenApprovedSEC23A10484
downregulated
Acetaminophen results in decreased expression of SEC23A mRNA14q21.1
AcetaminophenApprovedSERPINA6866
downregulated
Acetaminophen results in decreased expression of SERPINA6 mRNA14q32.13
AcetaminophenApprovedSMOX54498
upregulated
Acetaminophen results in increased expression of SMOX mRNA20p13
AcetaminophenApprovedSQLE6713
downregulated
Acetaminophen results in decreased expression of SQLE mRNA8q24.13
AcetaminophenApprovedSRSF16426
downregulated
Acetaminophen results in decreased expression of SRSF1 mRNA17q22
AcetaminophenApprovedSTRBP55342
downregulated
Acetaminophen results in decreased expression of STRBP mRNA9q33.1-q33.3
AcetaminophenApprovedTFDP17027
downregulated
Acetaminophen results in decreased expression of TFDP1 mRNA13q34
AcetaminophenApprovedTM9SF110548
downregulated
Acetaminophen results in decreased expression of TM9SF1 mRNA14q12
AcetaminophenApprovedTMEM9727346
downregulated
Acetaminophen results in decreased expression of TMEM97 mRNA17q11.2
AcetaminophenApprovedUQCRC27385
downregulated
Acetaminophen results in decreased expression of UQCRC2 mRNA16p12.2
CaffeineApprovedACAT239
downregulated
Caffeine results in decreased expression of ACAT2 mRNA6q25.3
CaffeineApprovedACIN122985
upregulated
Caffeine results in increased expression of ACIN1 mRNA14q11.2
CaffeineApprovedACSL32181
upregulated
Caffeine results in increased expression of ACSL3 mRNA2q36.1
CaffeineApprovedALDH18A15832
downregulated
Caffeine results in decreased expression of ALDH18A1 mRNA10q24.1
CaffeineApprovedANG283
downregulated
Caffeine results in decreased expression of ANG mRNA14q11.2
CaffeineApprovedARL6IP123204
upregulated
Caffeine results in increased expression of ARL6IP1 mRNA16p12.3
CaffeineApprovedATP5J29551
downregulated
Caffeine results in decreased expression of ATP5J2 mRNA7q22.1
CaffeineApprovedCALU813
downregulated
Caffeine results in decreased expression of CALU mRNA7q32.1
CaffeineApprovedCDK41019
downregulated
Caffeine results in decreased expression of CDK4 mRNA12q14.1
CaffeineApprovedCYC11537
downregulated
Caffeine results in decreased expression of CYC1 mRNA8q24.3
CaffeineApprovedDAD11603
downregulated
Caffeine results in decreased expression of DAD1 mRNA14q11.2
CaffeineApprovedEIF110209
upregulated
Caffeine results in increased expression of EIF1 mRNA17q21.2
CaffeineApprovedGLRX2745
downregulated
Caffeine results in decreased expression of GLRX mRNA5q15
CaffeineApprovedGLT8D155830
downregulated
Caffeine results in decreased expression of GLT8D1 mRNA3p21.1
CaffeineApprovedGLUD12746
downregulated
Caffeine results in decreased expression of GLUD1 mRNA10q23.2
CaffeineApprovedGSTO19446
downregulated
Caffeine results in decreased expression of GSTO1 mRNA10q25.1
CaffeineApprovedIGFBP13484
upregulated
Caffeine results in increased expression of IGFBP1 mRNA7p12.3
CaffeineApprovedLDHA3939
downregulated
Caffeine results in decreased expression of LDHA mRNA11p15.1
CaffeineApprovedMGST14257
downregulated
Caffeine results in decreased expression of MGST1 mRNA12p12.3
CaffeineApprovedMT1G4495
upregulated
Caffeine results in increased expression of MT1G mRNA16q13
CaffeineApprovedOAT4942
upregulated
Caffeine results in increased expression of OAT mRNA10q26.13
CaffeineApprovedPRELID127166
downregulated
Caffeine results in decreased expression of PRELID1 mRNA5q35.3
CaffeineApprovedPSME310197
downregulated
Caffeine results in decreased expression of PSME3 mRNA17q21.31
CaffeineApprovedRPS6KA36197
downregulated
Caffeine results in decreased expression of RPS6KA3 mRNAXp22.12
CaffeineApprovedRRS123212
upregulated
Caffeine results in increased expression of RRS1 mRNA8q13.1
CaffeineApprovedSCFD123256
downregulated
Caffeine results in decreased expression of SCFD1 mRNA14q12
CaffeineApprovedSEC136396
downregulated
Caffeine results in decreased expression of SEC13 mRNA3p25.3
CaffeineApprovedSEC23A10484
downregulated
Caffeine results in decreased expression of SEC23A mRNA14q21.1
CaffeineApprovedSERPINA6866
downregulated
Caffeine results in decreased expression of SERPINA6 mRNA14q32.13
CaffeineApprovedSMOX54498
upregulated
Caffeine results in increased expression of SMOX mRNA20p13
CaffeineApprovedSQLE6713
downregulated
Caffeine results in decreased expression of SQLE mRNA8q24.13
CaffeineApprovedSRSF16426
downregulated
Caffeine results in decreased expression of SRSF1 mRNA17q22
CaffeineApprovedSTRBP55342
downregulated
Caffeine results in decreased expression of STRBP mRNA9q33.1-q33.3
CaffeineApprovedTFDP17027
downregulated
Caffeine results in decreased expression of TFDP1 mRNA13q34
CaffeineApprovedTM9SF110548
downregulated
Caffeine results in decreased expression of TM9SF1 mRNA14q12
CaffeineApprovedTMEM9727346
downregulated
Caffeine results in decreased expression of TMEM97 mRNA17q11.2
CaffeineApprovedUQCRC27385
downregulated
Caffeine results in decreased expression of UQCRC2 mRNA16p12.2