Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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. Unsupervised gene expression analysis resulted in a characteristic molecular signature for each toxin, and a supervised analysis identified 31 outlier genes as distinct molecular signatures distinguishing carcinogens from noncarcinogens. Further analysis and multi-classification revealed 430 genes as surrogate markers for predicting carcinogenic potencies of each PAH with 100% accuracy. Our results suggest that these expression signatures can be used as predictable and discernible surrogate markers for detecting and predicting PAH exposure, and their carcinogenic potential. Furthermore, the use of these markers can be more widely applied in combination with traditional techniques for assessing and predicting toxic exposure to PAHs.
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PMID:Identification of molecular signatures predicting the carcinogenicity of polycyclic aromatic hydrocarbons (PAHs). 2257 12

Growing evidence indicates that changes in microRNA (miRNA) expression in cancer induced by chemical carcinogens play an important role in cancer development and progression by regulating related genes. However, the mechanisms underlying miRNA involvement in hepatocarcinogenesis induced by polycyclic aromatic hydrocarbons (PAHs) remain unclear. Thus, the identification of aberrant miRNA expression during PAH-induced cancer cell migration will lead to a better understanding of the substantial role of miRNAs in cancer progression. In the present study, miRNA expression profiling showed significant upregulation of miR-181a, -181b, and -181d in human hepatocellular carcinoma cells (HepG2 line) exposed to benzo[a]anthracene (BA) and benzo[k]fluoranthene (BF). MAPK phosphatase-5 (MKP-5), a validated miR-181 target that deactivates MAPKs, was markedly suppressed while phosphorylation of p38 MAPK was increased after BA and BF exposure. The migration of HepG2 cells, observed using the scratch wound-healing assay, also increased in a dose-dependent manner. Depletion of miR-181 family members by miRNA inhibitors enhanced the expression of MKP-5 and suppressed the phosphorylation of p38 MAPK. Furthermore, the depletion of the miR-181 family inhibited cancer cell migration. Based on these results, we conclude that the miR-181 family plays a critical role in PAH-induced hepatocarcinogenesis by targeting MKP-5, resulting in the regulation of p38 MAPK activation.
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PMID:Polycyclic aromatic hydrocarbon (PAH)-mediated upregulation of hepatic microRNA-181 family promotes cancer cell migration by targeting MAPK phosphatase-5, regulating the activation of p38 MAPK. 2399 76

Ozone is widely used in food processing, for example, to decompose mycotoxins or pesticide residues, to extend the shelf life of products, and for sanitation. The objective of this study was to assess the possibility of expanding the application of ozone for oxidative degradation of polycyclic aromatic hydrocarbons (PAHs). The evaluation was conducted by ozonation of a benzo[a]pyrene (BaP) standard solution and smoked fish (sprats) contaminated with PAHs. The effect of ozonation was immediate in the BaP solution; 89% of this toxic compound was decomposed after only 1 min of treatment. However, the impact of ozonation on the smoked sprats was less pronounced, even after prolonged treatment. The final reduction in benzo[b]fluoranthene and BaP concentrations in smoked sprats contaminated with PAHs was 34 and 46%, respectively, after 60 min of ozonation, but no significant decrease of benzo[a]anthracene and chrysene concentrations was observed. To evaluate the safety of ozonation, the toxicity of the ozone-treated BaP standard solution was investigated. In vitro toxicity was evaluated using human hepatocellular carcinoma and mouse embryonic fibroblast cell lines as models. The cytotoxicity of the BaP standard solution significantly increased after ozonation, indicating a pronounced negative effect in terms of food safety.
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PMID:Efficacy of Ozonation Treatments of Smoked Fish for Reducing Its Benzo[a]pyrene Concentration and Toxicity. 2822 59


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