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Azoxymethane-induced colorectal tumorigenesis in hypertensive rat models

ABSTRACT: To compare the tumor susceptibility between the hypertensive Dahl salt-sensitive rats (S) rat and S.LEW(10)x12x2x3x5 (S.LEW) congenic strain, one of the S.LEW congenic strains our laboratory previously constructed on rat chromosome 10 [Hypertension. 2007 Nov;50(5):891-8], Azoxymethane (AOM)-induced colon tumorigenesis in rats was assessed. At six weeks of age, both S and S.LEW congenic rats received intraperitoneal (IP) injection of AOM in sterial saline at a dose of 15mg/kg body weight once a week for two consecutive weeks. At 30 weeks of age, all the rats were euthanized through carbon dioxide inhalation. The colon tissue was harvested, dissected longitudinally, and washed with saline. The number and size of the colon tumors were recorded. We found that the total number of colon tumors was significantly higher in the S.LEW congenic strain compared with the S rat. To further study the genetic and molecular mechanisms causing the higher tumor susceptibility in the S.LEW congenic strain, we have employed the whole genome microarray expression profiling to identify genes and signaling pathways that are differential between the S and S.LEW congenic strain.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE75280 | GEO | 2016/04/04

SECONDARY ACCESSION(S): PRJNA303066

REPOSITORIES: GEO

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Azoxymethane-induced colorectal tumorigenesis in hypertensive rat models

Project description:To compare the tumor susceptibility between the hypertensive Dahl salt-sensitive rats (S) rat and S.LEW(10)x12x2x3x5 (S.LEW) congenic strain, one of the S.LEW congenic strains our laboratory previously constructed on rat chromosome 10 [Hypertension. 2007 Nov;50(5):891-8], Azoxymethane (AOM)-induced colon tumorigenesis in rats was assessed. At six weeks of age, both S and S.LEW congenic rats received intraperitoneal (IP) injection of AOM in sterial saline at a dose of 15mg/kg body weight once a week for two consecutive weeks. At 30 weeks of age, all the rats were euthanized through carbon dioxide inhalation. The colon tissue was harvested, dissected longitudinally, and washed with saline. The number and size of the colon tumors were recorded. We found that the total number of colon tumors was significantly higher in the S.LEW congenic strain compared with the S rat. To further study the genetic and molecular mechanisms causing the higher tumor susceptibility in the S.LEW congenic strain, we have employed the whole genome microarray expression profiling to identify genes and signaling pathways that are differential between the S and S.LEW congenic strain. At six weeks of age, both S and S.LEW congenic rats received intraperitoneal (IP) injection of AOM in serial saline at a dose of 15mg/kg body weight once a week for two consecutive weeks. At 30 weeks of age, all the rats were euthanized through carbon dioxide inhalation. The colon tissue was harvested, dissected longitudinally, and washed with saline. RNA from the harvested colons of 3 S and 3 S.LEW congenic rats were prepared for the microarray study.

2016-04-04 | E-GEOD-75280 | biostudies-arrayexpress

Global colorectal cancer gene expression in rats

Project description:The rat models of colorectal cancer (CRC), such as the azoxymethane (AOM) cancer-inducing model, are important tools for researching cancer initiation pathways. However, there is limited understanding of the expression pathways of underlying normal rat colonic epithelium and how this relates to human colonic epithelium. The aim of this study was to study the acute effects of AOM on the gene and pathway expression of the rat's colonic epithelium, whilst contrasting the background normal global expression patterns along the length of the rat as compared to the normal human colonic epithelium. The study used microarrays to investigate global gene expression of the colonic epithelium from proximal and distal sections of AOM- and saline (normal)-treated Sprague Dawley rats. Rat gene and pathway expression patterns were then compared in-silico with human microarray data (see GSE9254 for files) from normal tissue samples originating from proximal and distal regions of the colon.

2010-06-16 | E-GEOD-15184 | biostudies-arrayexpress

Renal Expression of Dahl SS/Jr (S) and Congenic Rats after 24 hours of Dietary Salt Loading

Project description:The overlap of congenic regions in an earlier substitution mapping study suggested the location of two blood pressure quantitative trait loci (QTL)-containing regions in the q-terminus of rat chromosome 3, QTL1 and the more distal, QTL2. Male SS/jr rats and two congenic substrain rats S.R(D3Mco36-D3Mco46) and S.R(D3Mco36-D3Got166) were maintained on a low salt (0.4% NaCl Harlan Teklad diet TD7034) diet until 39-41 days of age. These 3 rat strains will be hereafter referred to as S, S.R(ET3x1), and S.R(ET3x2), respectively. At 39-41 days of age, half of the rats from each strain were fed a high (4% NaCl Harlan Teklad diet TD83033) salt diet and water ad libitum for 24 hours. Both congenic substrains carry SR/jr (R)-rat alleles for QTL2 on an S-rat genetic background, while S.R(ET3x2) also carries R-rat alleles for QTL1. Renal gene expression analysis was used to identify differentially expressed genes or genes with altered activity within the S.R(ET3x2) congenic region. Keywords: strain differences in response to dietary changes

2015-08-28 | GSE12424 | GEO

Effect of DES-treated Ept congenic rat lines on gene expression in the anterior pituitary gland.

Project description:Anterior pituitary glands were isolated from 21 week old male rats treated for 12 weeks with the synthetic estrogen diethylstilbestrol (DES). Three biological replicates were prepared for each of 4 congenic lines: Ept1, Ept2, Ept6, and Ept9. Congenic rat lines were constructed by introgressing COP alleles onto an ACI background within a given Ept locus. Expression profiles were determined using Affymetrix Rat Genome 230 v. 2.0 arrays. Comparison of congenic rats with the ACI and COP parental strains (see series GSE4028) will allow identification of genes whose expression is influenced by an estrogen-induced pituitary tumor (Ept) QTL. Keywords: Estrogen Response

2006-03-31 | GSE4080 | GEO

Renal Expression of Dahl SS/Jr (S) and Congenic Rats after 28 days of dietary salt elevation

Project description:The overlap of congenic regions in an earlier substitution mapping study suggested the location of two blood pressure quantitative trait loci (QTL)-containing regions in the q-terminus of rat chromosome 3, QTL1 and the more distal, QTL2. Male SS/jr rats and two congenic substrain rats S.R(D3Mco36-D3Mco46) and S.R(D3Mco36-D3Got166) were maintained on a low salt (0.4% NaCl Harlan Teklad diet TD7034) diet until 39-41 days of age and then fed an intermediate (2% NaCl Harlan Teklad diet TD94217) salt diet for 28 days. These 3 rat strains will be hereafter referred to as S, S.R(ET3x1), and S.R(ET3x2), respectively. Both congenic substrains carry SR/jr (R)-rat alleles for QTL2 on an S-rat genetic background, while S.R(ET3x2) also carries R-rat alleles for QTL1. Renal gene expression analysis was used to identify differentially expressed genes or genes with altered activity within the S.R(ET3x2) congenic region. Keywords: strain differences in response to dietary changes

2015-08-28 | GSE12423 | GEO

Expression data from polycystic kidney disease susceptible and resistant rat strains

Project description:To facilitate the search for genetic modifiers that modulate ARPKD disease progression and severity, we sought to generate a congenic rat model that carries the PCK Pkhd1 mutation but is resistant to the development of ARPKD. We transferred the Pkhd1 mutation from the PCK rat onto the genetic background of the FHH (Fawn-Hooded Hypertensive) rat. This newly developed strain, called FHH.Pkhd1, showed significant amelioration of renal disease, and delayed onset of biliary abnormalities. To initiate the exploration for genes and pathways that modulate susceptibility to renal cystogenesis, we investigated transcriptional changes in kidneys from PCK, SD, FHH and FHH.Pkhd1 rats by microarray analysis.

2012-01-01 | GSE33056 | GEO

Mapping of Three Genetic Determinants of Susceptibility to Estrogen-Induced Mammary Cancer within the Emca8 Locus on Rat Chromosome 5

Project description:We are using the ACI rat model of 17beta-estradiol induced mammary cancer to define the mechanisms through which estrogens contribute to breast cancer development; identify and functionally characterize the genetic variants that determine susceptibility; and define the hormone-gene-environment interactions that influence development of mammary cancer in this physiologically relevant rat model. Female ACI rats are uniquely susceptible to development of mammary cancer when treated continuously with physiologic levels of 17beta-estradiol. Induction of mammary cancer in female ACI rats occurs through a mechanism that is largely dependent upon estrogen receptor-alpha. Interval mapping analyses of progeny generated in intercrosses between susceptible ACI rats and resistant Brown Norway (BN) rats revealed seven quantitative trait loci (QTL), designated Emca3 (Estrogen-induced mammary cancer) through Emca9, each of which harbors one or more genetic determinants of mammary cancer susceptibility. Genes that reside within Emca8 on RNO5 and were differentially expressed between 17beta-estradiol treated ACI and ACI.BN-Emca8 congenic rats were identified as Emca8 candidates. Two groups of 17beta-estradiol treated female rats were compared. Five ACI and five BN.ACI-Emca8 rats were treated with 17beta-estradiol for 12 weeks. Total RNA was isolated from the mammary glands of these animals, labeled, and hybridized to Affymetrix Rat Genome 230 2.0 Arrays (Affymetrix Inc.). Significantly differentially expressed genes were found between these groups.

2013-02-08 | E-GEOD-39788 | biostudies-arrayexpress

Variation of mRNA and lncRNA expression after using AMD3100 in rat chronic allograft nephropathy model.

Project description:To investigate the variation of mRNA and lncRNA expression after using AMD3100 in rat chronic allograft nephropathy model (CAN) model, we have employed mRNA and lncRNA microarray expression profiling as a discovery platform to identify genes with the potential. CAN rat models were established using male Fisher 344 to Lewis rats. Rats in the experimental group(n=3) were treated with AMD3100 (1 mg/kg/day subcutaneously, 0–12 weeks), rats in the control group(n=3) were treated with saline. The kidney grafts were harvested 12 weeks after modeling for microarray analysis.

2018-05-08 | GSE114088 | GEO

Comparison of renal transcript levels in Dahl Salt-sensitive (S) rat with S.R congenic rat containing a BP QTL

Project description:Kidney samples from three Dahl Salt-sensitive S rats were compared with kidney samples from three S.R(9)x3A congenic rats. Keywords = Blood Pressure Keywords = Quantitative trait locus Keywords = QTL Keywords = hypertension Keywords = rat Keywords = congenic Keywords: parallel sample

2004-09-20 | GSE1775 | GEO

Fish oil/pectin temporally alters gene expression profiles in exfoliated rat colonocytes throughout oncogenesis

Project description:We have demonstrated that fish oil/pectin (FO/P) diets protect against colon cancer compared to corn oil/cellulose (CO/C) by upregulating apoptosis and suppressing proliferation. To elucidate the mechanisms whereby FO/P diets induce apoptosis and suppress proliferation during the tumorigenic process, we analyzed the temporal gene expression profiles from exfoliated rat colonocytes. KEYWORDS: Fish oil/pectin, pectin, exfoliated colonocytes, gene expression, apoptosis, colon cancer, chemoprevention Rats consumed diets containing FO/P or CO/C and were injected with azoxymethane (AOM, 2x, 15 mg/kg BW, s.c.). Feces collected at the initiation, aberrant crypt foci (ACF), and tumor stages of colon cancer (24 h (n=20), 7 wk (n=37), and 28 wk (n=28) after AOM injection, respectively) was used for poly A(+) RNA extraction. Gene expression signatures were determined using Codelink arrays.

2012-02-20 | E-GEOD-27266 | biostudies-arrayexpress

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