Project description:C57BL/6j mice were treated with polycyclic aromatic hydrocarbons (benzo(a)pyrene, 7,12-dimethylbenz(a)anthracene, and 2,3,7,8 tetrachlorodibenzo-p-dioxin) Cyp1a1 and Cyp1b1 deletion separately and in combination were evaluated relative to the intact WT mice
Project description:Assessing the potential carcinogenicity of human toxins represents an ongoing challenge. Chronic rodent bioassays predict human cancer risk with limited reliability, and are expensive and time-consuming. To identify alternative prediction methods, we evaluated a transcriptomics-based human in vitro model to classify carcinogens by their modes of action. The aim of this study was to determine the transcriptomic response and identify specific molecular signatures of polycyclic aromatic hydrocarbons (PAHs), which can be used as predictors of carcinogenicity of environmental toxins in human in vitro systems. We found that characteristic molecular signatures facilitate identification and prediction of carcinogens. To evaluate the change in gene expression levels, human hepatocellular carcinoma (HepG2) cells were exposed to nine different PAHs (benzo[a]pyrene, dibenzo[a,h]anthracene, 3-methylcholanthrene, naphthalene, chrysene, phenanthrene, benzo[a]anthracene, benzo[k]fluoranthene, and indeno[1,2,3-c,d]pyrene) for 48 h. Gene expression analysis was conducted using a 44K whole human genome microarray (Agilent Technologies, USA).
Project description:To gain deeper insight into the mechanism of toxicity, it is important to identify and characterize miRNAs profiles involved in responses to specific classes of toxicants in conjunction with their impact on gene expression levels. However, few reports have described the effects of toxicants on miRNA expression profiles. Taking into account the prominent role of miRNAs in cancer development, progression, cell cycle control, and proliferation-related processes, it is likely that miRNAs are involved in the toxic response induced by carcinogens. Polycyclic aromatic hydrocarbons (PAHs) are a well-characterized class of human carcinogens. In the present study, we documented the different expression profiles of miRNAs in environmental carcinogen-exposed HepG2 cells by miRNA microarray analysis. To evaluate the change in miRNA expression levels, human hepatocellular carcinoma (HepG2) cells were exposed to two PAHs (benzo[a]anthracene, benzo[k]fluoranthene) for 48 h. miRNA expression analysis was conducted using a 8x16k human miRNA microarray (Agilent Technologies, USA).
Project description:Polycyclic aromatic hydrocarbons (PAHs) are a class of hundreds of structurally similar chemicals ubiquitously present in our environment. They are created during the incomplete combustion of organic materials, such as oil, wood, tobacco, and charbroiled meat. As such, human exposure to mixtures of PAHs can occur through consumption of PAH-containing foods and water, inhalation of polluted air, or dermal contact. Several PAHs have been classified as carcinogenic to humans or probably carcinogenic to humans by the International Agency for Research on Cancer. The mice in this study were exposed to a mixture of 8 PAHs, benzo(a)pyrene, benz(a)anthracene, benzo(b)fluoranthene, benzo(ghi)perylene, benzo(k)fluoranthene, chrysene, dibenz(ah)anthracene, and indeno(123,cd)pyrene. In the present study, we sought to determine the dose-dependent changes in gene expression upon oral exposure to this PAH mixture in the lung tissue. Adult male MutaTMMouse were exposed to three doses of the mixture of 8 PAHs or vehicle control (olive oil) for 28 days and sacrificed three days after the final exposure.
Project description:Polycyclic aromatic hydrocarbons (PAHs) can alter gene expression by acting through the aryl hydrocarbon receptor (AHR). In a previous phenotypic screen of over 120 PAHs, we identified four PAHs that induce an ectopic caudal fin (called X-fin) in larval zebrafish: benzo[k]fluoranthene (BkF), dibenzo[b,k]fluoranthene, dibenzo[a,h]anthracene, and benzo[j]fluoranthene. We investigated several plausible mechanisms of X-fin formation using the most potent X-fin inducer, BkF. The X-fin phenotype was dependent on the AHR paralog Ahr2, and we performed RNA sequencing to identify altered gene expression patterns. Transcriptional profiles of distal trunk tissue, where the phenotype was manifest, were generated for animals exposed to 1% DMSO (control) or 12 μM BkF. Four time points of X-fin development were considered for transcriptomics: prior to visual emergence of X-fin (48 hpf), during manifestation of disrupted caudal fin fold development (60 and 72 hpf), and after emergence of X-fin (96 hpf).
Project description:Polycyclic aromatic hydrocarbons (PAHs) are a class of hundreds of structurally similar chemicals ubiquitously present in our environment. They are created during the incomplete combustion of organic materials, such as oil, wood, tobacco, and charbroiled meat. As such, human exposure to mixtures of PAHs can occur through consumption of PAH-containing foods and water, inhalation of polluted air, or dermal contact. Several PAHs have been classified as carcinogenic to humans or probably carcinogenic to humans by the International Agency for Research on Cancer. Benzo(b)fluoranthene is one such compound. In the present study, we sought to determine the dose-dependent changes in gene expression upon oral exposure to benz(a)anthracene in the lung, liver, and forestomach tissues. Adult male MutaTMMouse were exposed to three doses of Benzo(b)fluoranthene or vehicle control (olive oil) for 28 days and sacrificed three days after the final exposure.
Project description:Polycyclic aromatic hydrocarbons (PAHs) are a class of hundreds of structurally similar chemicals ubiquitously present in our environment. They are created during the incomplete combustion of organic materials, such as oil, wood, tobacco, and charbroiled meat. As such, human exposure to mixtures of PAHs can occur through consumption of PAH-containing foods and water, inhalation of polluted air, or dermal contact. Several PAHs have been classified as carcinogenic to humans or probably carcinogenic to humans by the International Agency for Research on Cancer. Benzo(k)fluoranthen is one such compound. In the present study, we sought to determine the dose-dependent changes in gene expression upon oral exposure to benz(a)anthracene in the lung, liver, and forestomach tissues. Adult male MutaTMMouse were exposed to three doses of benzo(k)fluoranthene or vehicle control (olive oil) for 28 days and sacrificed three days after the final exposure.
Project description:Polycyclic aromatic hydrocarbons (PAHs) are a class of hundreds of structurally similar chemicals ubiquitously present in our environment. They are created during the incomplete combustion of organic materials, such as oil, wood, tobacco, and charbroiled meat. As such, human exposure to mixtures of PAHs can occur through consumption of PAH-containing foods and water, inhalation of polluted air, or dermal contact. Several PAHs have been classified as carcinogenic to humans or probably carcinogenic to humans by the International Agency for Research on Cancer. The mice in this study were exposed to a mixture of 4 PAHs, benzo(a)pyrene, benz(a)anthracene, benzo(b)fluoranthene, and chrysene. In the present study, we sought to determine the dose-dependent changes in gene expression upon oral exposure to this PAH mixture in the lung tissue. Adult male MutaTMMouse were exposed to three doses of the mixture of 4 PAHs or vehicle control (olive oil) for 28 days and sacrificed three days after the final exposure.
Project description:We are presenting here the application of toxicogenomics in the evaluation of the toxic effects of three dioxin-like compounds, two Polycyclic aromatic hydrocarbons (PAHs), Benzo(a)pyrene, Benzo(k) fluoranthene and b-naphthoflavone on the developing zebrafish embryo. The main goal is to distinguish the pattern of action of the chemical compounds and their needs varying the times of exposure. The results suggest a variety of MoA for different dioxin-like compounds, probably related to the nature and number of benzene rings. About 5% genes were affected by the treatment. Gene ontology (GO) analyses show that these genes are involved in the oxidation-reduction process. Representatives of each GO functional groups were selected and quantified by real-time PCR to validate the microarray data and to differentiate the action of dioxin-like compounds studied.