PMID- 26685285
OWN - NLM
STAT- MEDLINE
DCOM- 20170907
LR  - 20181113
IS  - 1552-9924 (Electronic)
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 124
IP  - 7
DP  - 2016 Jul
TI  - A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link 
      Different POPs to Common Metabolic Diseases.
PG  - 1034-41
LID - 10.1289/ehp.1510308 [doi]
AB  - BACKGROUND: A number of epidemiological studies have identified statistical 
      associations between persistent organic pollutants (POPs) and metabolic diseases, 
      but testable hypotheses regarding underlying molecular mechanisms to explain 
      these linkages have not been published. OBJECTIVES: We assessed the underlying 
      mechanisms of POPs that have been associated with metabolic diseases; three 
      well-known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 
      2,2 ,4,4 ,5,5 -hexachlorobiphenyl (PCB 153), and 
      4,4 -dichlorodiphenyldichloroethylene (p,p -DDE)] were studied. We used advanced 
      database search tools to delineate testable hypotheses and to guide 
      laboratory-based research studies into underlying mechanisms by which this POP 
      mixture could produce or exacerbate metabolic diseases. METHODS: For our 
      searches, we used proprietary systems biology software (MetaCore/MetaDrug) to 
      conduct advanced search queries for the underlying interactions database, 
      followed by directional network construction to identify common mechanisms for 
      these POPs within two or fewer interaction steps downstream of their primary 
      targets. These common downstream pathways belong to various cytokine and 
      chemokine families with experimentally well-documented causal associations with 
      type 2 diabetes. CONCLUSIONS: Our systems biology approach allowed identification 
      of converging pathways leading to activation of common downstream targets. To our 
      knowledge, this is the first study to propose an integrated global set of 
      step-by-step molecular mechanisms for a combination of three common POPs using a 
      systems biology approach, which may link POP exposure to diseases. Experimental 
      evaluation of the proposed pathways may lead to development of predictive 
      biomarkers of the effects of POPs, which could translate into disease prevention 
      and effective clinical treatment strategies. CITATION: Ruiz P, Perlina A, Mumtaz 
      M, Fowler BA. 2016. A systems biology approach reveals converging molecular 
      mechanisms that link different POPs to common metabolic diseases. Environ Health 
      Perspect 124:1034-1041; http://dx.doi.org/10.1289/ehp.1510308.
FAU - Ruiz, Patricia
AU  - Ruiz P
AD  - Computational Toxicology and Methods Development Laboratory, Division of 
      Toxicology and Human Health Sciences, Agency for Toxic Substances and Disease 
      Registry, Atlanta, Georgia, USA.
FAU - Perlina, Ally
AU  - Perlina A
FAU - Mumtaz, Moiz
AU  - Mumtaz M
FAU - Fowler, Bruce A
AU  - Fowler BA
LA  - eng
PT  - Journal Article
DEP - 20151218
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Biomarkers)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Organic Chemicals)
RN  - 4M7FS82U08 (Dichlorodiphenyl Dichloroethylene)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - ZRU0C9E32O (2,4,5,2',4',5'-hexachlorobiphenyl)
SB  - IM
MH  - Biomarkers
MH  - Dichlorodiphenyl Dichloroethylene
MH  - Environmental Exposure/*statistics & numerical data
MH  - Environmental Pollutants/*toxicity
MH  - Humans
MH  - Metabolic Diseases/*chemically induced/epidemiology
MH  - Organic Chemicals/*toxicity
MH  - Polychlorinated Biphenyls/toxicity
MH  - *Systems Biology
PMC - PMC4937870
COIS- The authors declare they have no actual or potential competing financial 
      interests.
EDAT- 2015/12/20 06:00
MHDA- 2017/09/08 06:00
PMCR- 2016/07/01
CRDT- 2015/12/20 06:00
PHST- 2015/06/05 00:00 [received]
PHST- 2015/12/10 00:00 [accepted]
PHST- 2015/12/20 06:00 [entrez]
PHST- 2015/12/20 06:00 [pubmed]
PHST- 2017/09/08 06:00 [medline]
PHST- 2016/07/01 00:00 [pmc-release]
AID - ehp.1510308 [pii]
AID - 10.1289/ehp.1510308 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2016 Jul;124(7):1034-41. doi: 10.1289/ehp.1510308. Epub 
      2015 Dec 18.