PMID- 26772051
OWN - NLM
STAT- MEDLINE
DCOM- 20160629
LR  - 20180304
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 294
DP  - 2016 Mar 1
TI  - Effects of defined mixtures of persistent organic pollutants (POPs) on multiple 
      cellular responses in the human hepatocarcinoma cell line, HepG2, using high 
      content analysis screening.
PG  - 21-31
LID - S0041-008X(16)30001-1 [pii]
LID - 10.1016/j.taap.2016.01.001 [doi]
AB  - Persistent organic pollutants (POPs) are toxic substances, highly resistant to 
      environmental degradation, which can bio-accumulate and have long-range 
      atmospheric transport potential. Most studies focus on single compound effects, 
      however as humans are exposed to several POPs simultaneously, investigating 
      exposure effects of real life POP mixtures on human health is necessary. A 
      defined mixture of POPs was used, where the compound concentration reflected its 
      contribution to the levels seen in Scandinavian human serum (total mix). Several 
      sub mixtures representing different classes of POPs were also constructed. The 
      perfluorinated (PFC) mixture contained six perfluorinated compounds, brominated 
      (Br) mixture contained seven brominated compounds, chlorinated (Cl) mixture 
      contained polychlorinated biphenyls and also 
      p,p'-dichlorodiphenyldichloroethylene, hexachlorobenzene, three chlordanes, three 
      hexachlorocyclohexanes and dieldrin. Human hepatocarcinoma (HepG2) cells were 
      used for 2h and 48h exposures to the seven mixtures and analysis on a 
      CellInsight NXT High Content Screening platform. Multiple cytotoxic endpoints 
      were investigated: cell number, nuclear intensity and area, mitochondrial mass 
      and membrane potential (MMP) and reactive oxygen species (ROS). Both the Br and 
      Cl mixtures induced ROS production but did not lead to apoptosis. The PFC mixture 
      induced ROS production and likely induced cell apoptosis accompanied by the 
      dissipation of MMP. Synergistic effects were evident for ROS induction when cells 
      were exposed to the PFC+Br mixture in comparison to the effects of the individual 
      mixtures. No significant effects were detected in the Br+Cl, PFC+Cl or total 
      mixtures, which contain the same concentrations of chlorinated compounds as the 
      Cl mixture plus additional compounds; highlighting the need for further 
      exploration of POP mixtures in risk assessment.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Wilson, Jodie
AU  - Wilson J
AD  - Institute for Global Food Security, School of Biological Sciences, Queen's 
      University Belfast, Northern Ireland, United Kingdom.
FAU - Berntsen, Hanne Friis
AU  - Berntsen HF
AD  - Norwegian University of Life Sciences, Oslo, Norway.
FAU - Zimmer, Karin Elisabeth
AU  - Zimmer KE
AD  - Norwegian University of Life Sciences, Oslo, Norway.
FAU - Frizzell, Caroline
AU  - Frizzell C
AD  - Institute for Global Food Security, School of Biological Sciences, Queen's 
      University Belfast, Northern Ireland, United Kingdom.
FAU - Verhaegen, Steven
AU  - Verhaegen S
AD  - Norwegian University of Life Sciences, Oslo, Norway.
FAU - Ropstad, Erik
AU  - Ropstad E
AD  - Norwegian University of Life Sciences, Oslo, Norway.
FAU - Connolly, Lisa
AU  - Connolly L
AD  - Institute for Global Food Security, School of Biological Sciences, Queen's 
      University Belfast, Northern Ireland, United Kingdom. Electronic address: 
      l.connolly@qub.ac.uk.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160107
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Complex Mixtures)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Fluorocarbons)
RN  - 0 (Hydrocarbons, Brominated)
RN  - 0 (Hydrocarbons, Chlorinated)
RN  - 0 (Organic Chemicals)
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Cell Survival/drug effects
MH  - Complex Mixtures/toxicity
MH  - Environmental Pollutants/*toxicity
MH  - Fluorocarbons/toxicity
MH  - Hep G2 Cells
MH  - High-Throughput Screening Assays
MH  - Humans
MH  - Hydrocarbons, Brominated/toxicity
MH  - Hydrocarbons, Chlorinated/toxicity
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mitochondria, Liver/drug effects/ultrastructure
MH  - Organic Chemicals/*toxicity
MH  - Oxidative Stress/drug effects
MH  - Reactive Oxygen Species/metabolism
OTO - NOTNLM
OT  - Cytotoxicity
OT  - High content analysis
OT  - Mixtures
OT  - Persistent organic pollutants
EDAT- 2016/01/17 06:00
MHDA- 2016/06/30 06:00
CRDT- 2016/01/17 06:00
PHST- 2015/10/08 00:00 [received]
PHST- 2015/12/10 00:00 [revised]
PHST- 2016/01/02 00:00 [accepted]
PHST- 2016/01/17 06:00 [entrez]
PHST- 2016/01/17 06:00 [pubmed]
PHST- 2016/06/30 06:00 [medline]
AID - S0041-008X(16)30001-1 [pii]
AID - 10.1016/j.taap.2016.01.001 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2016 Mar 1;294:21-31. doi: 10.1016/j.taap.2016.01.001. 
      Epub 2016 Jan 7.