Gene expression changes associated with cytotoxicity identified using cDNA arrays.
Article Details
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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
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Acetaminophen Approved ACAT2 39 downregulated Acetaminophen results in decreased expression of ACAT2 mRNA 6q25.3 Acetaminophen Approved ACIN1 22985 upregulated Acetaminophen results in increased expression of ACIN1 mRNA 14q11.2 Acetaminophen Approved ACSL3 2181 upregulated Acetaminophen results in increased expression of ACSL3 mRNA 2q36.1 Acetaminophen Approved ALDH18A1 5832 downregulated Acetaminophen results in decreased expression of ALDH18A1 mRNA 10q24.1 Acetaminophen Approved ANG 283 downregulated Acetaminophen results in decreased expression of ANG mRNA 14q11.2 Acetaminophen Approved ARL6IP1 23204 upregulated Acetaminophen results in increased expression of ARL6IP1 mRNA 16p12.3 Acetaminophen Approved ATP5J2 9551 downregulated Acetaminophen results in decreased expression of ATP5J2 mRNA 7q22.1 Acetaminophen Approved CALU 813 downregulated Acetaminophen results in decreased expression of CALU mRNA 7q32.1 Acetaminophen Approved CDK4 1019 downregulated Acetaminophen results in decreased expression of CDK4 mRNA 12q14.1 Acetaminophen Approved CYC1 1537 downregulated Acetaminophen results in decreased expression of CYC1 mRNA 8q24.3 Acetaminophen Approved DAD1 1603 downregulated Acetaminophen results in decreased expression of DAD1 mRNA 14q11.2 Acetaminophen Approved EIF1 10209 upregulated Acetaminophen results in increased expression of EIF1 mRNA 17q21.2 Acetaminophen Approved GLRX 2745 downregulated Acetaminophen results in decreased expression of GLRX mRNA 5q15 Acetaminophen Approved GLT8D1 55830 downregulated Acetaminophen results in decreased expression of GLT8D1 mRNA 3p21.1 Acetaminophen Approved GLUD1 2746 downregulated Acetaminophen results in decreased expression of GLUD1 mRNA 10q23.2 Acetaminophen Approved GSTO1 9446 downregulated Acetaminophen results in decreased expression of GSTO1 mRNA 10q25.1 Acetaminophen Approved IGFBP1 3484 upregulated Acetaminophen results in increased expression of IGFBP1 mRNA 7p12.3 Acetaminophen Approved LDHA 3939 downregulated Acetaminophen results in decreased expression of LDHA mRNA 11p15.1 Acetaminophen Approved MGST1 4257 downregulated Acetaminophen results in decreased expression of MGST1 mRNA 12p12.3 Acetaminophen Approved MT1B 4490 upregulated Acetaminophen results in increased expression of MT1B mRNA 16q13 Acetaminophen Approved MT1G 4495 upregulated Acetaminophen results in increased expression of MT1G mRNA 16q13 Acetaminophen Approved MT1H 4496 upregulated Acetaminophen results in increased expression of MT1H mRNA 16q13 Acetaminophen Approved OAT 4942 upregulated Acetaminophen results in increased expression of OAT mRNA 10q26.13 Acetaminophen Approved PRELID1 27166 downregulated Acetaminophen results in decreased expression of PRELID1 mRNA 5q35.3 Acetaminophen Approved PSME3 10197 downregulated Acetaminophen results in decreased expression of PSME3 mRNA 17q21.31 Acetaminophen Approved RPS6KA3 6197 downregulated Acetaminophen results in decreased expression of RPS6KA3 mRNA Xp22.12 Acetaminophen Approved RRS1 23212 upregulated Acetaminophen results in increased expression of RRS1 mRNA 8q13.1 Acetaminophen Approved SCFD1 23256 downregulated Acetaminophen results in decreased expression of SCFD1 mRNA 14q12 Acetaminophen Approved SEC13 6396 downregulated Acetaminophen results in decreased expression of SEC13 mRNA 3p25.3 Acetaminophen Approved SEC23A 10484 downregulated Acetaminophen results in decreased expression of SEC23A mRNA 14q21.1 Acetaminophen Approved SERPINA6 866 downregulated Acetaminophen results in decreased expression of SERPINA6 mRNA 14q32.13 Acetaminophen Approved SMOX 54498 upregulated Acetaminophen results in increased expression of SMOX mRNA 20p13 Acetaminophen Approved SQLE 6713 downregulated Acetaminophen results in decreased expression of SQLE mRNA 8q24.13 Acetaminophen Approved SRSF1 6426 downregulated Acetaminophen results in decreased expression of SRSF1 mRNA 17q22 Acetaminophen Approved STRBP 55342 downregulated Acetaminophen results in decreased expression of STRBP mRNA 9q33.1-q33.3 Acetaminophen Approved TFDP1 7027 downregulated Acetaminophen results in decreased expression of TFDP1 mRNA 13q34 Acetaminophen Approved TM9SF1 10548 downregulated Acetaminophen results in decreased expression of TM9SF1 mRNA 14q12 Acetaminophen Approved TMEM97 27346 downregulated Acetaminophen results in decreased expression of TMEM97 mRNA 17q11.2 Acetaminophen Approved UQCRC2 7385 downregulated Acetaminophen results in decreased expression of UQCRC2 mRNA 16p12.2 Caffeine Approved ACAT2 39 downregulated Caffeine results in decreased expression of ACAT2 mRNA 6q25.3 Caffeine Approved ACIN1 22985 upregulated Caffeine results in increased expression of ACIN1 mRNA 14q11.2 Caffeine Approved ACSL3 2181 upregulated Caffeine results in increased expression of ACSL3 mRNA 2q36.1 Caffeine Approved ALDH18A1 5832 downregulated Caffeine results in decreased expression of ALDH18A1 mRNA 10q24.1 Caffeine Approved ANG 283 downregulated Caffeine results in decreased expression of ANG mRNA 14q11.2 Caffeine Approved ARL6IP1 23204 upregulated Caffeine results in increased expression of ARL6IP1 mRNA 16p12.3 Caffeine Approved ATP5J2 9551 downregulated Caffeine results in decreased expression of ATP5J2 mRNA 7q22.1 Caffeine Approved CALU 813 downregulated Caffeine results in decreased expression of CALU mRNA 7q32.1 Caffeine Approved CDK4 1019 downregulated Caffeine results in decreased expression of CDK4 mRNA 12q14.1 Caffeine Approved CYC1 1537 downregulated Caffeine results in decreased expression of CYC1 mRNA 8q24.3 Caffeine Approved DAD1 1603 downregulated Caffeine results in decreased expression of DAD1 mRNA 14q11.2 Caffeine Approved EIF1 10209 upregulated Caffeine results in increased expression of EIF1 mRNA 17q21.2 Caffeine Approved GLRX 2745 downregulated Caffeine results in decreased expression of GLRX mRNA 5q15 Caffeine Approved GLT8D1 55830 downregulated Caffeine results in decreased expression of GLT8D1 mRNA 3p21.1 Caffeine Approved GLUD1 2746 downregulated Caffeine results in decreased expression of GLUD1 mRNA 10q23.2 Caffeine Approved GSTO1 9446 downregulated Caffeine results in decreased expression of GSTO1 mRNA 10q25.1 Caffeine Approved IGFBP1 3484 upregulated Caffeine results in increased expression of IGFBP1 mRNA 7p12.3 Caffeine Approved LDHA 3939 downregulated Caffeine results in decreased expression of LDHA mRNA 11p15.1 Caffeine Approved MGST1 4257 downregulated Caffeine results in decreased expression of MGST1 mRNA 12p12.3 Caffeine Approved MT1G 4495 upregulated Caffeine results in increased expression of MT1G mRNA 16q13 Caffeine Approved OAT 4942 upregulated Caffeine results in increased expression of OAT mRNA 10q26.13 Caffeine Approved PRELID1 27166 downregulated Caffeine results in decreased expression of PRELID1 mRNA 5q35.3 Caffeine Approved PSME3 10197 downregulated Caffeine results in decreased expression of PSME3 mRNA 17q21.31 Caffeine Approved RPS6KA3 6197 downregulated Caffeine results in decreased expression of RPS6KA3 mRNA Xp22.12 Caffeine Approved RRS1 23212 upregulated Caffeine results in increased expression of RRS1 mRNA 8q13.1 Caffeine Approved SCFD1 23256 downregulated Caffeine results in decreased expression of SCFD1 mRNA 14q12 Caffeine Approved SEC13 6396 downregulated Caffeine results in decreased expression of SEC13 mRNA 3p25.3 Caffeine Approved SEC23A 10484 downregulated Caffeine results in decreased expression of SEC23A mRNA 14q21.1 Caffeine Approved SERPINA6 866 downregulated Caffeine results in decreased expression of SERPINA6 mRNA 14q32.13 Caffeine Approved SMOX 54498 upregulated Caffeine results in increased expression of SMOX mRNA 20p13 Caffeine Approved SQLE 6713 downregulated Caffeine results in decreased expression of SQLE mRNA 8q24.13 Caffeine Approved SRSF1 6426 downregulated Caffeine results in decreased expression of SRSF1 mRNA 17q22 Caffeine Approved STRBP 55342 downregulated Caffeine results in decreased expression of STRBP mRNA 9q33.1-q33.3 Caffeine Approved TFDP1 7027 downregulated Caffeine results in decreased expression of TFDP1 mRNA 13q34 Caffeine Approved TM9SF1 10548 downregulated Caffeine results in decreased expression of TM9SF1 mRNA 14q12 Caffeine Approved TMEM97 27346 downregulated Caffeine results in decreased expression of TMEM97 mRNA 17q11.2 Caffeine Approved UQCRC2 7385 downregulated Caffeine results in decreased expression of UQCRC2 mRNA 16p12.2