Discrimination of genotoxic and non-genotoxic hepatocarcinogens by statistical analysis based on gene expression profiling in the mouse liver as determined by quantitative real-time PCR

被引：32

作者：

Watanabe, Takashi ^{[1
]}

Suzuki, Takayoshi ^{[12
]}

Natsume, Masakatsu ^{[2
]}

Nakajima, Madoka ^{[2
]}

Narumi, Kazunori ^{[3
]}

Hamada, Shuichi ^{[3
]}

Sakuma, Tomohiro ^{[4
]}

Koeda, Akiko ^{[5
]}

Oshida, Keiyu ^{[6
]}

Miyamoto, Yohei ^{[6
]}

Maeda, Akihisa ^{[6
]}

Hirayama, Michiasa ^{[7
]}

Sanada, Hisakazu ^{[8
]}

Honda, Hiroshi ^{[9
]}

Ohyama, Wakako ^{[10
]}

Okada, Emiko ^{[10
]}

Fujiishi, Yohei ^{[10
]}

Sutou, Shizuyo ^{[11
]}

Tadakuma, Ayami ^{[1
]}

Ishikawa, Yasuyoshi ^{[1
]}

Kido, Mahoko ^{[1
]}

Minamiguchi, Rina ^{[1
]}

Hanahara, Izumi ^{[1
]}

Furihata, Chie ^{[1
,12
]}

机构：

[1] Aoyama Gakuin Univ, Sch Sci & Engn, Funct Genom Lab, Chuo Ku, Sagamihara, Kanagawa 2525258, Japan

[2] Biosafety Res Ctr, Publ Interest Inc Fdn, Genotoxicol Lab Safety Assessment Unit, Shizuoka 4371213, Japan

[3] Mitsubishi Chem Medience Corp, Dept Safety Assessment, Ibaraki 3140255, Japan

[4] Japan Food Res Labs, Tama Ku, Tokyo 2060025, Japan

[5] Ina Res Inc, Ina, Nagano 3994501, Japan

[6] Toray Industries Ltd, Pharmaceut Res Labs, Toxicol & Pharmacokinet Labs, Kamakura, Kanagawa 2488555, Japan

[7] Mat Safety Test Ctr, Fujifilm Corp, Minamiashigara, Kanagawa 2500193, Japan

[8] Kaken Pharmaceut Co Ltd, Fujieda, Shizuoka 4268646, Japan

[9] Kao Corp, Tochigi Res Labs, Ichikai, Tochigi 3213497, Japan

[10] Yakult Cent Inst Microbiol Res, Kunitachi, Tokyo 1868650, Japan

[11] Shujitsu Univ, Sch Pharm, Naka Ku, Okayama, Tokyo 1868650, Japan

[12] Natl Inst Hlth Sci, Div Cellular & Gene Therapy Prod, Setagaya Ku, Tokyo 1588501, Japan

来源：

MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS | 2012年 / 747卷 / 02期

关键词：

Gene expression; Quantitative real-time PCR; PCA; Gene network; Mouse liver; REPLICATIVE DNA-SYNTHESIS; RAT-LIVER; IN-VIVO; COMET ASSAY; COLORECTAL-CANCER; TRANSGENIC MICE; MUTA(TM) MOUSE; SYNTHESIS RDS; MUTAGENICITY; LACZ;

D O I：

10.1016/j.mrgentox.2012.04.011

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The general aim of the present study is to discriminate between mouse genotoxic and non-genotoxic hepatocarcinogens via selected gene expression patterns in the liver as analyzed by quantitative real-time PCR (qPCR) and statistical analysis. qPCR was conducted on liver samples from groups of 5 male, 9-week-old B6C3F(1) mice, at 4 and 48 h following a single intraperitoneal administration of chemicals. We quantified 35 genes selected from our previous DNA microarray studies using 12 different chemicals: 8 genotoxic hepatocarcinogens (2-acetylaminofluorene, 2,4-diaminotoluene, diisopropanolnitrosamine, 4-dimethylaminoazobenzene, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, N-nitrosomorpholine, quinoline and urethane) and 4 non-genotoxic hepatocarcinogens (1,4-dichlorobenzene, dichlorodiphenyltrichloroethane, di(2-ethylhexyl)phthalate and furan). A considerable number of genes exhibited significant changes in their gene expression ratios (experimental group/control group) analyzed statistically by the Dunnett's test and Welch's t-test. Finally, we distinguished between the genotoxic and non-genotoxic hepatocarcinogens by statistical analysis using principal component analysis (PCA) of the gene expression profiles for 7 genes (Btg2, Ccnf, Ccng1, Lpr1, Mbd1, Phlda3 and Tubb2c) at 4 h and for 12 genes (Aen, Bax, Btg2, Ccnf, Ccng1, Cdkn1a, Gdf15, Lrp1, Mbd1, Phlda3, Plk2 and Tubb2c) at 48 h. Seven major biological processes were extracted from the

引用

页码：164 / 175

页数：12

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