Cytochrome P450 1 (CYP1) is an important enzyme family involved in the metabolism of pollutants, and used as a biomarker to monitor environmental pollution. In this study, a fluorescence-labeled cyp1a zebrafish line, named as KI (cyp1a-T2A-mCherry) (KICM), was originally constructed to monitor dioxin-like compounds in the environment. However, the cyp1a gene expression in the KICM line was inhibited by the fluorescence labeling, thus leading to a significantly increased sensitivity of KICM zebrafish line to PAHs. Then, a cyp1a knockout zebrafish line, named KOC, were constructed for comparative analysis with the cyp1a low-expression line. Interestingly, knockout of the cyp1a gene did not increase the sensitivity of zebrafish to PAHs as significantly as the cyp1a low-expression line. So, the expression levels of related genes in the aryl hydrocarbon receptor pathway were analyzed and the results showed that the expression level of cyp1b in KOC group was significantly higher than that of wild type and KICM under the same PAH exposure. This indicated that the effect of losing cyp1a was compensated by inducing expression of cyp1b. In conclusion, two new zebrafish models including cyp1a low-expression line and cyp1a knockout line were constructed in this study, which may provide a convenient model for subsequent studies on the toxicity mechanism of PAHs and the role of cyp1a in detoxification.
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http://dx.doi.org/10.1016/j.gene.2023.147391 | DOI Listing |
Gene
June 2023
College of Marine Sciences, South China Agricultural University, Guangzhou, Guangdong, 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, 510642, China. Electronic address:
Cytochrome P450 1 (CYP1) is an important enzyme family involved in the metabolism of pollutants, and used as a biomarker to monitor environmental pollution. In this study, a fluorescence-labeled cyp1a zebrafish line, named as KI (cyp1a-T2A-mCherry) (KICM), was originally constructed to monitor dioxin-like compounds in the environment. However, the cyp1a gene expression in the KICM line was inhibited by the fluorescence labeling, thus leading to a significantly increased sensitivity of KICM zebrafish line to PAHs.
View Article and Find Full Text PDFChem Res Toxicol
April 2019
State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment , Nanjing University, Nanjing , China.
Hydroxylation of polyaromatic compounds through cytochromes P450 (CYPs) is known to result in potentially estrogenic transformation products. Recently, there has been an increasing awareness of the importance of alternative pathways such as aldehyde oxidases (AOX) or N-methyltransferases (NMT) in bioactivation of small molecules, particularly N-heterocycles. Therefore, this study investigated the biotransformation and activity of methylated quinolines, a class of environmentally relevant N-heterocycles that are no native ligands of the estrogen receptor (ER), in the estrogen-responsive cell line ERα CALUX.
View Article and Find Full Text PDFSci Total Environ
November 2016
Department of Veterinary Sciences, University of Torino, Largo Braccini 2, Grugliasco, Italy. Electronic address:
PCDDs, PCDFs, and PCBs are persistent organic pollutants (POPs) that accumulate in animal products and may pose serious health problems. Those able to bind the aryl hydrocarbon receptor (AhR), eliciting a plethora of toxic responses, are defined dioxin-like (DL) compounds, while the remainders are called non-DL (NDL). An EFSA opinion has highlighted the tendency of ovine liver to specifically accumulate DL-compounds to a greater extent than any other farmed ruminant species.
View Article and Find Full Text PDFAquat Toxicol
November 2014
Department of Biological Sciences, University of Windsor, Windsor, Ontario, Canada N9B3P4. Electronic address:
The Brown bullhead (Ameiurus nebulosus) is able to survive and reproduce in high levels of environmentally contaminated areas of the Great Lakes. The purpose of this study was to establish whether there are adaptive genetic/molecular changes occurring in these fish that allow for their survival. Expression of a cell cycle regulator, p53 and the toxin metabolizing protein, CYP1A were measured in liver tissue from bullhead caught from either clean or contaminated areas of Lake Erie and surrounding areas.
View Article and Find Full Text PDFAquat Toxicol
January 2011
Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA.
Atlantic killifish (Fundulus heteroclitus) inhabiting the PCB-contaminated Superfund site in New Bedford Harbor (MA, USA) have evolved genetic resistance to the toxic effects of these compounds. They also lack induction of cytochrome P4501A (CYP1A) and other aryl hydrocarbon receptor (AHR)-dependent responses after exposure to AHR agonists, suggesting an overall down-regulation of the AHR signaling pathway. In this study, we hypothesized that the genetic resistance is due to altered AHR expression resulting from hypermethylation of DNA in the promoter region of AHR genes in fish inhabiting New Bedford Harbor.
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