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

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

“…Our results conˆrmed this. As in our previous advanced qPCR studies (8-10) we did not examine PAH, and we did not observe remarkable increases in these genes (8)(9)(10). It was reported that Cyp1a1 and Cyp1a2 were regulated by arylhydrocarbon receptor (AhR) (16).…”

“…Chrysene exhibited statistically signiˆcant increases of gene expression in 15 genes (Bax, Btg2, Casp1, Ccng1, Ccng2, Cdkn1a, Crp, Ephx1, Gdf15, Hmox1, Igfbp1, Lcn2, Mdm2, Phlda3 and Pmm1) and increase tendencies in 3 genes (Ddit4, Hspb1 and Pml) among these genes. However, the gene expression of Trp53 itself did not show changes from 4 to 48 h. In our previous studies (7)(8)(9)(10), the gene expression of Trp53 scarcely changed in the mouse and rat liver 4 and 48 h and 28 days after the administration of genotoxic and non-genotoxic hepatocarcinogens. The basal gene expression of Trp53 in the control animals may already be su‹cient for DNA damage under the present experimental conditions.…”

“…We recently successfully discriminated between 8 genotoxic mouse hepatocarcinogens (2-acetylamino‰uorene, 2,4-diaminotoluene, diisopropanolnitrosamine, 4-dimethylaminoazobenzen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, N-nitrosomorpholine, quinoline and urethane) and 4 non-genotoxic hepatocarcinogens (1,4-dichlorobenzene, dichlorodiphenyltrichloroethane, DEHP and furan) using qPCR with 35 candidate genes and principal component analysis (PCA) for 12 selected genes associated with Trp53-mediated signaling pathway involved in the DNA damage response. This discrimination was demonstrated at 4 and 48 h after a single administration of the chemicals (9). More recently, we succeeded in applying a similar study in rat liver.…”

“…RNA isolation: The total RNA was extracted from approximately 30 mg from each liver using Micro Igfbp1 GATCAGCCCATCCTGTGGAACG TTCTCGTTGGCAGGGCTCCTTC 32 Jun GCCAAGAACTCGGACCTTCTC AGTGGTGATGTGCCCATTGCTG 33 Lcn2 CACCACGGACTACAACCAGTTC GCTCCTTGGTTCTTCCATACAG 34 Lpp CCGTGATTTC CATGTGCACT GC CT TGGCCGTCAA GACCCTGATG 35 Lrp1 GGGCCATGAATGTGGAAATTGG GTGGCATACACTGGGTTGGTG 36 Ly6a CTTGTGGCCCTACTGTGTGCAG GGGCAGGTAATTGATGGGCAAG 37 Mbd1 GGATCCTGACACTCAAGAATGG GTTTGGGCTAACACAGGAAGAG 38 Mdm2 TTGATCCGAGCCTGGGTCTGTG AAGATCCTGATGCGAGGGCGTC 39 Phlda3 TGGCTGGAACGCTCAGATCAC TTAGGACACAAGGGTCCCAGTC 40 Plk2 CTGTTGAGAGCGTCTTCAGTTG CCATAGTTCACAGTTAAGCAGC 41 Pml GGCAAGAAGCGTCCTTACCTTC GGACAGCAACAGCAGTTCAGTC 42 Pmm1 TCTCCCGAGGAGGCATGATAAG CAAAGTCATTCCCGCCAGGAC 43 Ppp1r3c TGGAAACCTGACGGAGTGCAG GCAAGCCTTGGACTGCCAAAG 44 Psma3 GATCGACCCATCAGGTGTTTC CACGGCAAGTCATTTCCTTCATCTG 45 Rad52 TGACGCCACTCACCAGAGGAAG GCTGGAAGTACCGCATGCTTGG 46 Rcan1 GGTCCACGTGTGTGAGAGTG TGGATGGGTGTGTACTCCGG 47 St3gal5 GCAGGTCATGCACAATGTGACC CTGGGTGAGGTTTGCCGTGTTC 48 Trp53 TTGGACCCTGGCACCTACAATG GCAGACAGGCTTTGCAGAATGG 49 Tubb2a CGAGCTGACCCAGCAGATGTTC CACGGCCGTCTTGACGTTGTTG 50 Tubb4b TTGGCAACAGCACCGCTATTC TCGGACACCAGGTCGTTCATG Smash MS-100 (Tomy Digital Biology Co., Ltd., Tokyo, Japan) and QuickGene-800 (Fujiˆlm, Tokyo, Japan) as described previously (8,9). Quantiˆcation by qPCR: The complementary DNA (cDNA) was obtained from the total RNA using the SuperScript First strand synthesis system for RT-PCR kit (Invitrogen Corp., Carlsbad, CA, USA) (8).…”

Research of the intracranial neoplasia cell sensitivity to chemotherapy drugs

“…3г). В последние годы МГК находит применение в он-кологии, главным образом для оценки общей или без-рецидивной выживаемости онкологических пациентов в зависимости от экспрессии маркерных генов [15,20,21] или предсказания чувствительности, устойчивости неопластических клеток к химиопрепаратам [8]. J.M.…”