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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Gräns, Johanna Johansson, Junko Michelová, Marie Wassmur, Britt Norström, Elisabeth Wallin, Margareta Celander, Malin C. |
| Description | Country affiliation: Sweden Author Affiliation: Gräns J ( Department of Biological and Environmental Sciences, University of Gothenburg, Box 463, SE 405 30 Gothenburg, Sweden.); Johansson J ( Department of Biological and Environmental Sciences, University of Gothenburg, Box 463, SE 405 30 Gothenburg, Sweden.); Michelová M ( Department of Biological and Environmental Sciences, University of Gothenburg, Box 463, SE 405 30 Gothenburg, Sweden.); Wassmur B ( Department of Biological and Environmental Sciences, University of Gothenburg, Box 463, SE 405 30 Gothenburg, Sweden.); Norström E ( Department of Biological and Environmental Sciences, University of Gothenburg, Box 463, SE 405 30 Gothenburg, Sweden.); Wallin M ( Department of Biological and Environmental Sciences, University of Gothenburg, Box 463, SE 405 30 Gothenburg, Sweden.); Celander MC ( Department of Biological and Environmental Sciences, University of Gothenburg, Box 463, SE 405 30 Gothenburg, Sweden. Electronic address: malin.celander@gu.se.) |
| Abstract | The cytochrome P450 1A (CYP1A) biomarker response was studied in the Poeciliopsis lucida hepatocellular carcinoma (PLHC-1) cell line, which represents a good model for studies on aryl hydrocarbon receptor (AhR) - CYP1A signaling. The PLHC-1 cells were exposed to the prototypical CYP1A inducer and AhR agonist ß-naphthoflavone (BNF) in combination with different azoles. Two imidazoles (clotrimazole and prochloraz) and two benzimidazoles (nocodazole and omeprazole) were used. Exposure to clotrimazole, prochloraz and nocodazole resulted in 2-4 fold induction of the CYP1A-mediated ethoxyresorufin-O-deethylase (EROD) activities at 24 and 48h, whereas exposure to the omeprazole for 48h had no effect on the EROD activity. Clotrimazole, nocodazole and prochloraz also acted as inhibitors of EROD activities in situ in PLHC-1 cells (IC50=1.3-7.7µM), whereas omeprazole had no effect on this activity (IC50=72µM). Exposure to 10µM prochloraz resulted in 3-fold induction of CYP1A mRNA and exposure to 10µM nocodazole resulted in 16-fold induction of CYP1A mRNA levels at 24h compared to controls. In the mixture experiments, more-than-additive mixture effects between BNF and the azoles clotrimazole, prochloraz and nocodazole on EROD activities were evident, with nocodazole showing the strongest mixture effect. The presence of nocodazole increased the response to BNF up to 200-fold on CYP1A mRNA and up to 16-fold on EROD activities and prolonged the effect of BNF exposure on EROD activities by 24h or longer. This suggests that azoles that are inhibitors and/or competing substrates for the CYP1A enzymes can cause increased sensitivity to exposures to chemicals that depend on CYP1A metabolism for their elimination in situations of mixed chemical exposures. The results also suggest that the EROD biomarker response can be significantly affected in azole-contaminated areas. The responsiveness of the EROD biomarker to BNF exposure was studied in PLHC-1 that had been pre-treated with nocodazole for 5 or 24h at concentrations that are known to disassemble microtubules at 24h in these cells. Pre-treatment of PLHC-1 cells with nocodazole for either 5 or 24h had no effect on the responsiveness to BNF exposure, which implies that the EROD activity can be induced in cells with disassembled microtubules. |
| File Format | HTM / HTML |
| ISSN | 0166445X |
| Volume Number | 164 |
| e-ISSN | 18791514 |
| Journal | Aquatic Toxicology |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2015-07-01 |
| Publisher Place | Netherlands |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Toxicology Azoles Toxicity Cytochrome P-450 Cyp1a1 Biosynthesis Beta-naphthoflavone Animals Biological Markers Metabolism Cell Line Cyprinodontiformes Genetics Drug Synergism Enzyme Induction Drug Effects Receptors, Aryl Hydrocarbon Agonists Water Pollutants, Chemical Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Health, Toxicology and Mutagenesis Aquatic Science |
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