PMID- 25911577
OWN - NLM
STAT- MEDLINE
DCOM- 20160303
LR  - 20181202
IS  - 1879-1514 (Electronic)
IS  - 0166-445X (Linking)
VI  - 164
DP  - 2015 Jul
TI  - Mixture effects between different azoles and beta-naphthoflavone on the CYP1A 
      biomarker in a fish cell line.
PG  - 43-51
LID - S0166-445X(15)00122-8 [pii]
LID - 10.1016/j.aquatox.2015.04.016 [doi]
AB  - 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 
      beta-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=1.3-7.7muM), 
      whereas omeprazole had no effect on this activity (IC50=72muM). Exposure to 10muM 
      prochloraz resulted in 3-fold induction of CYP1A mRNA and exposure to 10muM 
      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.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Grans, Johanna
AU  - Grans J
AD  - Department of Biological and Environmental Sciences, University of Gothenburg, 
      Box 463, SE 405 30 Gothenburg, Sweden.
FAU - Johansson, Junko
AU  - Johansson J
AD  - Department of Biological and Environmental Sciences, University of Gothenburg, 
      Box 463, SE 405 30 Gothenburg, Sweden.
FAU - Michelova, Marie
AU  - Michelova M
AD  - Department of Biological and Environmental Sciences, University of Gothenburg, 
      Box 463, SE 405 30 Gothenburg, Sweden.
FAU - Wassmur, Britt
AU  - Wassmur B
AD  - Department of Biological and Environmental Sciences, University of Gothenburg, 
      Box 463, SE 405 30 Gothenburg, Sweden.
FAU - Norstrom, Elisabeth
AU  - Norstrom E
AD  - Department of Biological and Environmental Sciences, University of Gothenburg, 
      Box 463, SE 405 30 Gothenburg, Sweden.
FAU - Wallin, Margareta
AU  - Wallin M
AD  - Department of Biological and Environmental Sciences, University of Gothenburg, 
      Box 463, SE 405 30 Gothenburg, Sweden.
FAU - Celander, Malin C
AU  - Celander MC
AD  - Department of Biological and Environmental Sciences, University of Gothenburg, 
      Box 463, SE 405 30 Gothenburg, Sweden. Electronic address: malin.celander@gu.se.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150414
PL  - Netherlands
TA  - Aquat Toxicol
JT  - Aquatic toxicology (Amsterdam, Netherlands)
JID - 8500246
RN  - 0 (Azoles)
RN  - 0 (Biomarkers)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Water Pollutants, Chemical)
RN  - 6051-87-2 (beta-Naphthoflavone)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
SB  - IM
MH  - Animals
MH  - Azoles/*toxicity
MH  - Biomarkers/metabolism
MH  - Cell Line
MH  - Cyprinodontiformes/genetics/metabolism
MH  - Cytochrome P-450 CYP1A1/*biosynthesis/genetics/metabolism
MH  - Drug Synergism
MH  - Enzyme Induction/drug effects
MH  - Receptors, Aryl Hydrocarbon/agonists
MH  - Water Pollutants, Chemical/toxicity
MH  - beta-Naphthoflavone/*toxicity
OTO - NOTNLM
OT  - Aryl hydrocarbon receptor
OT  - Combination effects
OT  - Cytochrome P450
OT  - Cytoskeleton
EDAT- 2015/04/26 06:00
MHDA- 2016/03/05 06:00
CRDT- 2015/04/26 06:00
PHST- 2014/12/18 00:00 [received]
PHST- 2015/04/08 00:00 [revised]
PHST- 2015/04/12 00:00 [accepted]
PHST- 2015/04/26 06:00 [entrez]
PHST- 2015/04/26 06:00 [pubmed]
PHST- 2016/03/05 06:00 [medline]
AID - S0166-445X(15)00122-8 [pii]
AID - 10.1016/j.aquatox.2015.04.016 [doi]
PST - ppublish
SO  - Aquat Toxicol. 2015 Jul;164:43-51. doi: 10.1016/j.aquatox.2015.04.016. Epub 2015 
      Apr 14.