Project description:To explore the possible changes of gene expression induced by a carcinogen, we treated wild-type and Dicer1-KO mice with one dose of 120 mg/kg N-ethyl-N-nitrosourea (ENU), a model genotoxic carcinogen, and vehicle control. The gene expression profiles were assessed in the mouse livers in wild-type and Dicer1-KO mice design. Total RNA were isolated from the livers at days 15 after the treatment and their expression was determined using Gene Array. Gene expression in treated wild-type and Dicer1-KO mice was measured at 15 days after exposure to one dose of 120 mg/kg N-ethyl-N-nitrosourea (ENU). Each treatment duplex ,Drug-ko-a,Drug-ko-b,Drug-wt-a,Drug-wt-b,Control-ko-a,Control-ko-b,Control-wt-a,Control-wt-b.
Project description:To explore the possible changes of gene expression induced by a carcinogen, we treated wild-type and Dicer1-KO mice with one dose of 120 mg/kg N-ethyl-N-nitrosourea (ENU), a model genotoxic carcinogen, and vehicle control. The gene expression profiles were assessed in the mouse livers in wild-type and Dicer1-KO mice design. Total RNA were isolated from the livers at days 15 after the treatment and their expression was determined using Gene Array.
Project description:Dysregulated expression of microRNA (miRNA) has been extensively detected in human cancer tissues and has shown promise in defining tumor status. It, however, is little known whether and when expression of miRNAs can be changed in normal tissues after carcinogen exposure. To explore possible time-course changes of miRNA expression induced by carcinogens, we treated mice with one dose of 120 mg/kg body weight model genotoxic carcinogen N-ethyl-N-nitrosourea (ENU) and vehicle control. The miRNA expression profiles were determined in the mouse livers in a time-course manner. MiRNAs were isolated from the livers of ENU-treated and control mice at days 1, 3, 7, 15, 30 and 120 after the treatment. The miRNA expressions were determined using RT2-mouse miRNA PCR Array. Principal component analysis of the gene expression profiles showed that miRNA expression at post-treatment days 7 and 15 were different from those at the other time points and the controls. The numbers of the dysregulated miRNAs changed with time, being 3, 5, 14, 32, 5 and 5 at post-treatment days 1, 3, 7, 15, 30 and 120, respectively. Functional analysis of the differentially expressed miRNA at post-treatment days 7 and 15 indicated that the major functions of these ENU-induced dysregulated miRNAs were mainly associated with DNA repair and tumorigenesis, suggesting the microRNA expression is related to genotoxicity of ENU. These results propose that one to two weeks after ENU exposure is the best time for miRNA expression sampling; and that a large number of miRNAs whose expression is dysregulated after carcinogen exposure could be an indicator for carcinogenic damage. Series type: Non-coding RNA profiling by RT-PCR
Project description:To further our investigations for early biomarkers of non-genotoxic carcinogenesis, groups of mice were treated by gavage with a prototypic non-genotoxic carcinogen: Phenobarbital (PB, CAS: 57-30-7), for a period of 28 and 90d and liver tissue harvested for expression profiling. Control groups were treated with appropriate vehicle (0.5% Methylcellulose).
Project description:Rapidly increasing number of man-made chemicals urges the development of reliable time- and cost-effective approaches for the carcinogen detection and identification. Considering this, the utility of high throughput microarray gene expression profiling for the identification of genotoxic and non-genotoxic carcinogens in vitro was investigated. Human terminally differentiated hepatic HepaRG cells were treated with model liver carcinogens, genotoxic carcinogen aflatoxin B1 (AFB1) and non-genotoxic carcinogen methapyrilene, at IC10 and IC25 concentrations for 72 hours, and transcriptomic profiles were determined. Treatment of HepaRG cells with IC10 and IC25 concentrations of AFB1 resulted in altered expression of 538 and 3033 genes (p-value ≤0.01 and fold change ≥2.0), respectively, and treatment of HepaRG cells with methapyrilene at the IC10 and IC25 concentrations altered the expression of 1255 and 1861 genes, respectively. Pathway analysis of transcriptomic signatures in HepaRG cells treated with minimally cytotoxic IC10 concentrations of AFB1 and methapyrilene demonstrated a strong enrichment in genes involved in key carcinogen-associated pathways, including receptor-mediated effects, detoxification response, cell death and apoptosis, cell proliferation and survival, oxidative stress and inflammation. Importantly, DNA damage and repair, cell cycle progression, and cell cycle checkpoint control pathways were uniquely activated in AFB1-treated HepaRG cells, whereas receptor-mediated signaling detoxification response pathway was predominantly altered in methapyrilene-treated HepaRG cells. In summary, high throughput microarray gene expression approach identifies specific carcinogen-exposure-associated transcriptomic responses and identifies affected molecular pathways, and categorize pathways associated with carcinogen exposure in a short-term in vitro test.
Project description:Dynamic changes in the mouse liver DNA methylome associated with short (1 day) and prolonged (7, 28 and 91 days) exposure to the rodent liver non-genotoxic carcinogen (NGC), phenobarbital (PB). Full expression dataset (all time points: 1, 7, 28, 91 days) Replicated control vs. pb treated study
Project description:The expression of NRF2 was activated in human hepatocellular carcinoma. In current study, we observed that in hepatic carcinogen diethylnitrosamine induced liver tumor mouse model, NRF2 knockout mouse developed less liver tumor incidence than wild type mouse. To reveal the detailed mechanism, RNA-seq experiment was conducted to compare gene transcriptome profiles of NRF2 WT and KO mice during HCC progression.
Project description:Acute effects caused by the non-genotoxic carcinogen and peroxisome proliferator (PP) diethylhexylphthalate (DEHP) in the mouse liver
Project description:Acute effects caused by the non-genotoxic carcinogen and peroxisome proliferator (PP) diethylhexylphthalate (DEHP) in the mouse liver Mice (n = 6) were dosed by oral gavage (10 ml/kg body weight) with the non-genotoxic carcinogen diethylhexylphthalate (DEHP), every 24 h for 3 days (1150 mg/kg/day), or with an equivalent volume of vehicle control (corn oil).
