Mechanisms of hepatic cancer by persistent organic pollutants

• Published in: Current opinion in toxicology Vol. 19; pp. 105 - 111
• Main Authors: Klaunig, James E., Melo, Luma, Tilmant, Karen
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-02-2020
• Subjects: Adverse outcome pathway; Aryl hydrocarbon receptor; Constitutive androstane receptor; Molecular initiating events; Peroxisome proliferator–activated receptor alpha; Persistent organic pollutants; Molecular initiating events; Aryl hydrocarbon receptor; Peroxisome proliferator–activated receptor alpha; Persistent organic pollutants; Constitutive androstane receptor; Adverse outcome pathway
• ISSN: 2468-2020; 2468-2020
• DOI: 10.1016/j.cotox.2020.02.001

Persistent organic pollutants (POPs) are a group of organic chemicals, as defined by the Stockholm Convention that are persistent in the environment and accumulate in organisms including humans. Most POPs are restricted in use or no longer manufactured because of this persistence, bioaccumulation, and toxicity. In addition, an association between POP exposure and human disease has been suggested. Regarding toxicological effects and particularly cancer, most POPs have been shown to induce hepatic tumors when chronically administered to rodents. Understanding the mechanisms by which POPs induce liver cancer is important in developing meaningful human cancer risk evaluation to these compounds. In this article, we have reviewed the probable mechanisms of hepatic cancer induced by POPs mode of action and molecular initiating events and the relationship of these mechanisms to potential human cancer risk.
•Rodent liver tumors induced by many POP chemicals function through a nuclear receptor activation.•Hepatocarcinogenic POP chemicals that activate CAR or PPAR alpha have limited human cancer risk.•Hepatocarcinogenic POP chemicals that activate Ahr or induce cytotoxicity may have human relevance.•Dose and exposure considerations are important in assessing potential human risk.