ABSTRACT: Transcriptional Response of Male MutaTMMouse Hippocampus to Benzo[a]pyrene (BaP; CAS no. 50-32-8, now also known as benzo[pqr]tetraphene) Exposure
Project description:Benzo(a)pyrene is a well-established human carcinogen in humans and rodents. In the present study, we sought to determine the dose- and time-dependent changes in gene expression upon oral exposure to benzo(a)pyrene. Adult male MutaTMMouse were exposed to three doses of benzo(a)pyrene or vehicle control (olive oil) for 28 days and sacrificed three days after the final exposure. This experiment examined the forestomach transcriptional response of male mice exposed to BaP for 28 days at three different doses, including D1 (25 mg/kg BW/day), D2 (50 mg/kg BW/day), and D3 (75 mg/kg BW/day) and vehicle control. Each dose group was examined 72 hours following the final exposure. Each dose group and time point had 4-5 biological replicates. There were a total 17 samples (arrays) included in the final analysis using a two-colour reference design.
Project description:We performed microarray-based expression profiling on liver of male zebrafish exposed to 5, 50, and 500 µg/L of benzo-[A]-pyrene (BAP) for 24 and 96 hours, to identify global transcriptional programs and biological pathways involved in BAP-induced adaptive responses under in vivo environment.
Project description:Benzo(a)pyrene is a well-established human carcinogen in humans and rodents. In the present study, we sought to determine the dose- and time-dependent changes in gene expression upon oral exposure to benzo(a)pyrene. Adult male MutaTMMouse were exposed to three doses of benzo(a)pyrene or vehicle control (olive oil) for 28 days and sacrificed three days after the final exposure.
Project description:In this study, we investigate mRNA profiles in lung of mice exposed to benzo(a)pyrene. Male mice were exposed to three doses (25, 50, and 75 mg/kg/day BaP) for 28 days and profiles were examined three days post-exposure. Our analyses reveal that BaP causes pulmonary specific cellular transformation indicative of carcinogenesis.
Project description:Human colon carcinoma cells (HCT116) differing in p53 status were exposed to benzo(a)pyrene (BaP) (2.5 and 5 uM for up to 48 h) or anti-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide (BPDE)(0.5 and 1 uM for up to 24 h), and their gene expression responses compared by cDNA microarray technology. Keywords: BaP or BPDE exposure
Project description:Lack of change in microRNA expression in adult mouse liver following treatment with benzo(a)pyrene (BaP), as detected using Agilent miRNA arrays. We have investigated the effect of exposure to 150 mg/kg benzo(a)pyrene (BaP) for 3 days on mRNA and miRNA expression levels in adult mouse liver. We used Agilent miRNA array platforms to assess effects of BaP exposure on miRNA expression levels. Our results indicate a distinct lack of effect of BaP of miRNA expression, despite widespread changes in mRNA levels. Keywords: Toxicology, miRNA
Project description:We performed microarray-based expression profiling on liver of male zebrafish exposed to 5, 50, and 500 µg/L of benzo-[A]-pyrene (BAP) for 24 and 96 hours, to identify global transcriptional programs and biological pathways involved in BAP-induced adaptive responses under in vivo environment. We analyzed 34 arrays of BAP-treated adult male zebrafish liver and 15 arrays of control fish.
Project description:Lack of change in microRNA expression in adult mouse liver following treatment with benzo(a)pyrene (BaP), as detected using Exiqon miRNA arrays. Adult male mice were exposed to 150 mg/kg benzo(a)pyrene (BaP) or solvent for 3 days and sampled 4 hours after the last dose. MicroRNA expression levels in adult mouse liver were measured using Exiqon miRNA arrays. Our results indicate a distinct lack of effect of BaP of miRNA expression, despite widespread changes in mRNA levels (measured using Agilent arrays). Lack of miRNA changes was confirmed with Agilent miRNA arrays. Keywords: Toxicology, miRNA
Project description:Benzo[a]pyrene (BaP) is a genotoxic carcinogen and a neurotoxicant. The neurotoxicity of BaP is proposed to arise from either genotoxicity leading to neuronal cell death, or perturbed expression of N-methyl-D-aspartate receptor (NMDAR) subunits. To explore these hypotheses, we profiled hippocampal gene expression of adult male MutaTMMouse administered 1, 35, or 70 mg BaP/kg bw per day by oral gavage for three days, by RNA-Sequencing (RNA-Seq), DNA microarrays, and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) 24 hr post-exposure. RNA-Seq revealed altered expression of zero, 260, and 219 genes (p-value < 0.05, fold-change ≥ ± 1.5) following exposure to the low, medium, and high doses, respectively; 54 genes were confirmed using microarrays. Microarray and RT-PCR analysis showed increased expression of NMDAR subunits Grina and Grin2a. In contrast, no effects on classical BaP targets, including xenobiotic metabolism and DNA-damage response genes, were found, despite comparable BaP-DNA adduct levels in the cerebellum to those detected in the lung and liver in previous studies. Meta-analysis revealed that BaP-induced transcriptional profiles most closely match those from the hippocampus of transgenic mice that share neurotoxicity observed in BaP-exposed mice (i.e., defects in learning). Overall, our results support that BaP-induced neurotoxicity is more likely to be a consequence of NMDAR perturbation than of genotoxicity, and identify other important genes potentially mediating this adverse outcome.
Project description:In this research, we used MeDIP-sequencing technology to detect genome-wide methylation changes in benzo[a]pyrene(BaP)-exposed zebrafish larvae. We identified differentially methylated genes are associated with many diseases, including development of brain, and central nervous system.This high-throughput sequencing could help us to understand new mechanisms of BaP toxicity.
