Time-course Comparison of Gene Expression Profiles Induced by the Genotoxic Hepatocarcinogen, Chrysene, in the Mouse Liver

Sakurai, Mikiya; Watanabe, Takashi; Suzuki, Takayoshi; Furihata, Chie

doi:10.3123/jemsge.2014.005

Cited by 9 publications

(11 citation statements)

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“…2 [ 41 ]. They also identified by qPCR that 4 and 48 h after administration were key time points from the time-dependent changes in gene expression during the acute phase (4 to 48 h) following the administration of chrysene [ 42 ]. Additionally, in rat liver, they successfully discriminated two GTHCs (DEN and 2,6-dinitrotoluene) from an NGTHC (DEHP) and an NGTNHC (phenacetin) at 4 and 48 h, as shown in Fig.…”

Section: Introductionmentioning

confidence: 99%

“…Only a few papers have been published on discriminating GTCs from NGTCs using RNA-Seq in vivo [8,9]. Therefore, this review also includes data on discriminating GTCs, NGTCs, and NHCs using DNA microarray and qPCR [36][37][38][39][40][41][42][43][44][45][46][47], as these data would be helpful in creating a toxicogenomics database. This review also incorporates recent reports on whole-transcriptome RNA-Seq on animals in vivo, in the liver, kidney, and other organs, although reports did not include the discrimination of GTCs from NGTCs .…”

Section: Introductionmentioning

confidence: 99%

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Short-term in vivo testing to discriminate genotoxic carcinogens from non-genotoxic carcinogens and non-carcinogens using next-generation RNA sequencing, DNA microarray, and qPCR

Furihata

Suzuki

2023

Genes and Environ

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Next-generation RNA sequencing (RNA-Seq) has identified more differentially expressed protein-coding genes (DEGs) and provided a wider quantitative range of expression level changes than conventional DNA microarrays. JEMS·MMS·Toxicogenomics group studied DEGs with targeted RNA-Seq on freshly frozen rat liver tissues and on formalin-fixed paraffin-embedded (FFPE) rat liver tissues after 28 days of treatment with chemicals and quantitative real-time PCR (qPCR) on rat and mouse liver tissues after 4 to 48 h treatment with chemicals and analyzed by principal component analysis (PCA) as statics. Analysis of rat public DNA microarray data (Open TG-GATEs) was also performed. In total, 35 chemicals were analyzed [15 genotoxic hepatocarcinogens (GTHCs), 9 non-genotoxic hepatocarcinogens (NGTHCs), and 11 non-genotoxic non-hepatocarcinogens (NGTNHCs)]. As a result, 12 marker genes (Aen, Bax, Btg2, Ccnf, Ccng1, Cdkn1a, Gdf15, Lrp1, Mbd1, Phlda3, Plk2, and Tubb4b) were proposed to discriminate GTHCs from NGTHCs and NGTNHCs. U.S. Environmental Protection Agency studied DEGs induced by 4 known GTHCs in rat liver using DNA microarray and proposed 7 biomarker genes, Bax, Bcmp1, Btg2, Ccng1, Cdkn1a, Cgr19, and Mgmt for GTHCs. Studies involving the use of whole-transcriptome RNA-Seq upon exposure to chemical carcinogens in vivo have also been performed in rodent liver, kidney, lung, colon, and other organs, although discrimination of GTHCs from NGTHCs was not examined. Candidate genes published using RNA-Seq, qPCR, and DNA microarray will be useful for the future development of short-term in vivo studies of environmental carcinogens using RNA-Seq.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Short-term in vivo testing to discriminate genotoxic carcinogens from non-genotoxic carcinogens and non-carcinogens using next-generation RNA sequencing, DNA microarray, and qPCR

Furihata

Suzuki

2023

Genes and Environ

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“…We first selected about 100 candidate marker genes to discriminate mouse genotoxic hepatocarcinogens from non-genotoxic hepatocarcinogens by DNA microarrays, which were next quantified by qPCR [ 9 ]. We extracted about 30 key genes from dose responses in gene expression [ 10 ] and selected key point times at the beginning and end of the acute phase (4 and 48 h) [ 11 ]. We successfully showed the discrimination of genotoxic and non-genotoxic hepatocarcinogens in mouse liver [ 12 ] and rat liver [ 13 ] by qPCR and the application of principal component analysis (PCA) at 4 and 48 h after administration of hepatocarcinogens.…”

Section: Introductionmentioning

confidence: 99%

“…We previously noticed that changes in gene expression were greater at 4 h, while reports on changes in the gene expression profile in rodent liver at the acute stage in the first 48 h after administration of a hepatocarcinogen were limited. We therefore selected key point times at 4 and 48 h from changes in time-dependent gene expression in mouse liver during the acute phase between 4 and 48 h after administration of chrysene, a polycyclic aromatic hydrocarbon (PAH) and genotoxic hepatocarcinogen, as determined by qPCR [ 11 ]. Chrysene (100 mg/kg bw) was injected intraperitoneally into groups of three 9-week-old B6C3F1 male mice, and 4, 16, 20, 24, and 48 h later, livers were dissected and processed for gene expression.…”

Section: Introductionmentioning

confidence: 99%

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Collaborative studies in toxicogenomics in rodent liver in JEMS·MMS; a useful application of principal component analysis on toxicogenomics

et al. 2016

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Toxicogenomics is a rapidly developing discipline focused on the elucidation of the molecular and cellular effects of chemicals on biological systems. As a collaborative study group of Toxicogenomics/JEMS·MMS, we conducted studies on hepatocarcinogens in rodent liver in which 100 candidate marker genes were selected to discriminate genotoxic hepatocarcinogens from non-genotoxic hepatocarcinogens. Differential gene expression induced by 13 chemicals were examined using DNA microarray and quantitative real-time PCR (qPCR), including eight genotoxic hepatocarcinogens [o-aminoazotoluene, chrysene, dibenzo[a,l]pyrene, diethylnitrosamine (DEN), 7,12-dimethylbenz[a]anthracene, dimethylnitrosamine, dipropylnitrosamine and ethylnitrosourea (ENU)], four non-genotoxic hepatocarcinogens [carbon tetrachloride, di(2-ethylhexyl)phthalate (DEHP), phenobarbital and trichloroethylene] and a non-genotoxic non-hepatocarcinogen [ethanol]. Using qPCR, 30 key genes were extracted from mouse livers at 4 h and 28 days following dose-dependent gene expression alteration induced by DEN and ENU: the most significant changes in gene expression were observed at 4 h. Next, we selected key point times at 4 and 48 h from changes in time-dependent gene expression during the acute phase following administration of chrysene by qPCR. We successfully showed discrimination of eight genotoxic hepatocarcinogens [2-acetylaminofluorene, 2,4-diaminotoluene, diisopropanolnitrosamine, 4-dimethylaminoazobenzene, 4-(methylnitsosamino)-1-(3-pyridyl)-1-butanone, N-nitrosomorpholine, quinoline and urethane] from four non-genotoxic hepatocarcinogens [1,4-dichlorobenzene, dichlorodiphenyltrichloroethane, DEHP and furan] using qPCR and principal component analysis. Additionally, we successfully identified two rat genotoxic hepatocarcinogens [DEN and 2,6-dinitrotoluene] from a nongenotoxic-hepatocarcinogen [DEHP] and a non-genotoxic non-hepatocarcinogen [phenacetin] at 4 and 48 h. The subsequent gene pathway analysis by Ingenuity Pathway Analysis extracted the DNA damage response, resulting from the signal transduction of a p53-class mediator leading to the induction of apoptosis. The present review of these studies suggests that application of principal component analysis on the gene expression profile in rodent liver during the acute phase is useful to predict genotoxic hepatocarcinogens in comparison to non-genotoxic hepatocarcinogens and/or non-carcinogenic hepatotoxins.

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Using RNA-Seq with 11 marker genes to evaluate 1,4-dioxane compared with typical genotoxic and non-genotoxic rat hepatocarcinogens

Furihata

Toyoda

Ogawa

et al. 2018

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Time-course Comparison of Gene Expression Profiles Induced by the Genotoxic Hepatocarcinogen, Chrysene, in the Mouse Liver

Cited by 9 publications

References 35 publications

Short-term in vivo testing to discriminate genotoxic carcinogens from non-genotoxic carcinogens and non-carcinogens using next-generation RNA sequencing, DNA microarray, and qPCR

Short-term in vivo testing to discriminate genotoxic carcinogens from non-genotoxic carcinogens and non-carcinogens using next-generation RNA sequencing, DNA microarray, and qPCR

Collaborative studies in toxicogenomics in rodent liver in JEMS·MMS; a useful application of principal component analysis on toxicogenomics

Using RNA-Seq with 11 marker genes to evaluate 1,4-dioxane compared with typical genotoxic and non-genotoxic rat hepatocarcinogens

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