PMID- 22099347
OWN - NLM
STAT- MEDLINE
DCOM- 20120316
LR  - 20151119
IS  - 1879-1514 (Electronic)
IS  - 0166-445X (Linking)
VI  - 105
IP  - 3-4 Suppl
DP  - 2011 Oct
TI  - Cocktail effects on biomarker responses in fish.
PG  - 72-7
LID - 10.1016/j.aquatox.2011.06.002 [doi]
AB  - One of today's greatest challenges in environmental toxicology is to understand 
      effects of mixture toxicity, commonly referred to as cocktail effects, in humans 
      and in wildlife. Biomarker responses in fish are routinely used to assess 
      exposure of anthropogenic chemicals in the aquatic environment. However, little 
      is known about how cocktail effects affect these biomarker responses. For this 
      reason, there is an obvious risk for misinterpretation of biomarker-data and this 
      can have profound negative effects on stakeholder's decisions and actions, as 
      well as on legislations and remediation-plans initiated in order to reduce 
      exposure to certain chemicals. Besides, chemical safety-levels are traditionally 
      based on experiences from lab-studies with single chemicals, which is unfortunate 
      as a chemical can be more toxic when it is mixed with other chemicals, because of 
      the cocktail effect. This review focuses on pharmacokinetic interactions between 
      different classes of pollutants on detoxification mechanisms and how that affects 
      two commonly used biomarkers in the aquatic environment: (1) induction of 
      cytochrome P450 1A (CYP1A) that is mediated via activation of the arylhydrocarbon 
      receptor (AhR), used to assess exposure to aromatic hydrocarbons; (2) induction 
      of vitellogenin (VTG) that is mediated via activation of the estrogen receptor 
      (ER), used to assess exposure to estrogenic chemicals. These responses can be 
      either directly or indirectly affected by the presence of other classes of 
      pollutants as a result of cocktail effects. For example, chemicals that inhibit 
      the function of key metabolic enzymes and transporter pumps that are involved in 
      elimination of AhR- and ER agonists, can result in bioaccumulation of aromatic 
      hydrocarbons and estrogenic chemicals resulting in increased biomarker responses. 
      This cocktail effect can lead to overestimation of the actual exposure pressure. 
      On the contrary, induction of expression of key metabolic enzymes and transporter 
      activities can result in increased elimination of AhR- and ER agonists that can 
      lead to possible underestimation of the exposure. Another type of cocktail effect 
      is inhibiting receptor cross-talk that may cause decreased biomarker responses 
      that can also lead to underestimation of the actual exposure. To address the 
      possible involvement of pharmacokinetic interactions including receptor 
      cross-talks, we need to combine analyses on receptor signaling with studies on 
      function of key biotransformation enzymes such as major catabolic CYP enzymes 
      (e.g. CYP1-4) as well as efflux pumps (e.g. ATP-binding cassette transporter 
      proteins). Besides, studies of inhibition of these enzymes and pumps activities 
      pose a great potential to be used as future biomarkers as they are more clearly 
      liked to adverse outcomes, compared to for example induction of CYP1A and VTG 
      expression.
CI  - 2011 Elsevier B.V. All rights reserved.
FAU - Celander, Malin C
AU  - Celander MC
AD  - University of Gothenburg, Department of Zoology, Box 463, SE-405 30 Gothenburg, 
      Sweden. malin.celander@zool.gu.se
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20110612
PL  - Netherlands
TA  - Aquat Toxicol
JT  - Aquatic toxicology (Amsterdam, Netherlands)
JID - 8500246
RN  - 0 (Biomarkers)
RN  - 0 (Complex Mixtures)
RN  - 0 (Estrogens)
RN  - 0 (Hydrocarbons, Aromatic)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Vitellogenins)
RN  - 0 (Water Pollutants, Chemical)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
SB  - IM
MH  - Animals
MH  - Biomarkers/*metabolism
MH  - Complex Mixtures/metabolism/pharmacokinetics/toxicity
MH  - Cytochrome P-450 CYP1A1/metabolism
MH  - Estrogens/metabolism/pharmacokinetics/toxicity
MH  - Female
MH  - Fishes/*metabolism
MH  - Hydrocarbons, Aromatic/metabolism/pharmacokinetics/toxicity
MH  - *Inactivation, Metabolic
MH  - Male
MH  - Receptors, Aryl Hydrocarbon/metabolism
MH  - Receptors, Estrogen/metabolism
MH  - Vitellogenins/metabolism
MH  - Water Pollutants, Chemical/metabolism/*pharmacokinetics/*toxicity
EDAT- 2011/12/07 06:00
MHDA- 2012/03/17 06:00
CRDT- 2011/11/22 06:00
PHST- 2011/05/31 00:00 [received]
PHST- 2011/06/01 00:00 [accepted]
PHST- 2011/11/22 06:00 [entrez]
PHST- 2011/12/07 06:00 [pubmed]
PHST- 2012/03/17 06:00 [medline]
AID - S0166-445X(11)00160-3 [pii]
AID - 10.1016/j.aquatox.2011.06.002 [doi]
PST - ppublish
SO  - Aquat Toxicol. 2011 Oct;105(3-4 Suppl):72-7. doi: 10.1016/j.aquatox.2011.06.002. 
      Epub 2011 Jun 12.