Related Experiment Video
Updated: Mar 28, 2026

Experimental Protocol for Detecting Mitochondrial Function in Hepatocytes Exposed to Organochlorine Pesticides
Published on: September 16, 2020
A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic
Patricia Ruiz1, Ally Perlina, Moiz Mumtaz
1Computational Toxicology and Methods Development Laboratory, Division of Toxicology and Human Health Sciences, Agency for Toxic Substances and Disease Registry, Atlanta, Georgia, USA.
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.
Related Concept Videos
Types of Toxins
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
Toxic Reactions: Overview
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
Microbial Bioremediation of Pesticides
Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion
Pharmacogenetics of Drug Metabolism: Overview
Bioactivation and Tissue Toxicity

