Abstract
Organochlorine pesticides (OCPs) belong to a heterogeneous class of organic compounds blacklisted by the Stockholm Convention in 2009 due to their harmful impact on human health. Among OCPs, β-hexachlorocyclohexane (β-HCH) is one of the most widespread and, at the same time, poorly studied environmental contaminant. Due to its physicochemical properties, β-HCH is the most hazardous of all HCH isomers; therefore, clarifying the mechanisms underlying its molecular action could provide further elements to draw the biochemical profile of this OCP. For this purpose, LNCaP and HepG2 cell lines were used as models and were subjected to immunoblot, immunofluorescence, and RT-qPCR analysis to follow the expression and mRNA levels, together with the distribution, of key biomolecules involved in the intracellular responses to β-HCH. In parallel, variations in redox homeostasis and cellular bioenergetic profile were monitored to have a complete overview of β-HCH effects. Obtained results strongly support the hypothesis that β-HCH could be an endocrine disrupting chemical as well as an activator of AhR signaling, promoting the establishment of an oxidative stress condition and a cellular metabolic shift toward aerobic glycolysis. In this altered context, β-HCH can also induce DNA damage through H2AX phosphorylation, demonstrating its multifaceted mechanisms of action.
Highlights
Organochlorine pesticides (OCPs) represent 40% of total environmental pollutants and constitute a significant source of contamination all over the world
The cell lines used in this study (HepG2 and LNCaP) have suitable characteristics for testing the toxicological potential of β-HCH in all its facets, as well as being the same lines already employed as a model to demonstrate the hub role of STAT3 in the signaling pathways triggered by β-HCH
Data regarding a possible role of β-HCH as an endocrine-disrupting chemicals (EDCs) are scarce and controversial, shedding light on this mechanism could provide a further element to draw the toxicological profile of this substance
Summary
Organochlorine pesticides (OCPs) represent 40% of total environmental pollutants and constitute a significant source of contamination all over the world. In recent years, growing attention has been paid to the hexachlorocyclohexane (HCH), a chlorinated cyclic saturated hydrocarbon listed as “POP” (persistent organic pollutant) by the Stockholm Convention and banned in 2009 [2]. The industrial synthesis of hexachlorocyclohexane through the benzene photochlorination gives a mixture of isomers (α,β,γ,δ,ε) that structurally differ in the axial and equatorial orientation of the chlorine atoms with respect to the cyclohexane carbon ring. Among these isomers, only γ-HCH has specific insecticidal properties and it is referred to as lindane [3]. The extensive use of lindane as a commercial pesticide during the last 70 years is a heavy burden for human beings as well as the environment: 8–12 tons of undesired derivatives were produced for each ton of lindane, leading to an overall storage of almost 7.2 million tons of HCH waste isomers mostly buried in uncontrolled dumps at many sites around the world [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
