Analysis of cell death inducing compounds

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Analysis of cell death inducing compounds. / Spicker, Jeppe; Pedersen, Henrik Toft; Brunak, Søren; Nielsen, Henrik Bjørn.

In: Archives of Toxicology, Vol. 81, No. 11, 2007, p. 803-11.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Spicker, J, Pedersen, HT, Brunak, S & Nielsen, HB 2007, 'Analysis of cell death inducing compounds', Archives of Toxicology, vol. 81, no. 11, pp. 803-11. https://doi.org/10.1007/s00204-007-0207-4

APA

Spicker, J., Pedersen, H. T., Brunak, S., & Nielsen, H. B. (2007). Analysis of cell death inducing compounds. Archives of Toxicology, 81(11), 803-11. https://doi.org/10.1007/s00204-007-0207-4

Vancouver

Spicker J, Pedersen HT, Brunak S, Nielsen HB. Analysis of cell death inducing compounds. Archives of Toxicology. 2007;81(11):803-11. https://doi.org/10.1007/s00204-007-0207-4

Author

Spicker, Jeppe ; Pedersen, Henrik Toft ; Brunak, Søren ; Nielsen, Henrik Bjørn. / Analysis of cell death inducing compounds. In: Archives of Toxicology. 2007 ; Vol. 81, No. 11. pp. 803-11.

Bibtex

@article{2ce8d11189074f319c4cac0744f202f1,
title = "Analysis of cell death inducing compounds",
abstract = "Biomarkers for early detection of toxicity hold the promise of improving the failure rates in drug development. In the present study, gene expression levels were measured using full-genome RAE230 version 2 Affymetrix GeneChips on rat liver tissue 48 h after administration of six different compounds, three toxins (ANIT, DMN and NMF) and three non-toxins (Caeruelein, Dinitrophenol and Rosiglitazone). We identified three gene transcripts with exceptional predictive performance towards liver toxicity and/or changes in histopathology. The three genes were: glucokinase regulatory protein (GCKR), ornithine aminotransferase (OAT) and Cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase) (Cyp2C29). RT-PCR for these three genes was performed and four additional compounds were included for validation. The quantitative RT-PCR analysis confirmed the findings based on the microarray data and using the three genes a classification rate of 55 of 57 samples was achieved for the classification of not toxic versus toxic. The single most promising biomarker (OAT) alone resulted in a surprisingly 100% correctly classified samples. OAT has not previously been linked to toxicity and cell death in the literature and the novel finding represents a putative hepatotoxicity biomarker.",
author = "Jeppe Spicker and Pedersen, {Henrik Toft} and S{\o}ren Brunak and Nielsen, {Henrik Bj{\o}rn}",
year = "2007",
doi = "10.1007/s00204-007-0207-4",
language = "English",
volume = "81",
pages = "803--11",
journal = "Archives of Toxicology",
issn = "0340-5761",
publisher = "Springer",
number = "11",

}

RIS

TY - JOUR

T1 - Analysis of cell death inducing compounds

AU - Spicker, Jeppe

AU - Pedersen, Henrik Toft

AU - Brunak, Søren

AU - Nielsen, Henrik Bjørn

PY - 2007

Y1 - 2007

N2 - Biomarkers for early detection of toxicity hold the promise of improving the failure rates in drug development. In the present study, gene expression levels were measured using full-genome RAE230 version 2 Affymetrix GeneChips on rat liver tissue 48 h after administration of six different compounds, three toxins (ANIT, DMN and NMF) and three non-toxins (Caeruelein, Dinitrophenol and Rosiglitazone). We identified three gene transcripts with exceptional predictive performance towards liver toxicity and/or changes in histopathology. The three genes were: glucokinase regulatory protein (GCKR), ornithine aminotransferase (OAT) and Cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase) (Cyp2C29). RT-PCR for these three genes was performed and four additional compounds were included for validation. The quantitative RT-PCR analysis confirmed the findings based on the microarray data and using the three genes a classification rate of 55 of 57 samples was achieved for the classification of not toxic versus toxic. The single most promising biomarker (OAT) alone resulted in a surprisingly 100% correctly classified samples. OAT has not previously been linked to toxicity and cell death in the literature and the novel finding represents a putative hepatotoxicity biomarker.

AB - Biomarkers for early detection of toxicity hold the promise of improving the failure rates in drug development. In the present study, gene expression levels were measured using full-genome RAE230 version 2 Affymetrix GeneChips on rat liver tissue 48 h after administration of six different compounds, three toxins (ANIT, DMN and NMF) and three non-toxins (Caeruelein, Dinitrophenol and Rosiglitazone). We identified three gene transcripts with exceptional predictive performance towards liver toxicity and/or changes in histopathology. The three genes were: glucokinase regulatory protein (GCKR), ornithine aminotransferase (OAT) and Cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase) (Cyp2C29). RT-PCR for these three genes was performed and four additional compounds were included for validation. The quantitative RT-PCR analysis confirmed the findings based on the microarray data and using the three genes a classification rate of 55 of 57 samples was achieved for the classification of not toxic versus toxic. The single most promising biomarker (OAT) alone resulted in a surprisingly 100% correctly classified samples. OAT has not previously been linked to toxicity and cell death in the literature and the novel finding represents a putative hepatotoxicity biomarker.

U2 - 10.1007/s00204-007-0207-4

DO - 10.1007/s00204-007-0207-4

M3 - Journal article

C2 - 17503021

VL - 81

SP - 803

EP - 811

JO - Archives of Toxicology

JF - Archives of Toxicology

SN - 0340-5761

IS - 11

ER -

ID: 40804778