Complex roles for sulfation in the toxicities of polychlorinated biphenyls

Abstract

Polychlorinated biphenyls (PCBs) are persistent organic toxicants derived from legacy pollution sources and their formation as inadvertent byproducts of some current manufacturing processes. Metabolism of PCBs is often a critical component in their toxicity, and relevant metabolic pathways usually include their initial oxidation to form hydroxylated polychlorinated biphenyls (OH-PCBs). Subsequent sulfation of OH-PCBs was originally thought to be primarily a means of detoxication; however, there is strong evidence that it may also contribute to toxicities associated with PCBs and OH-PCBs. These contributions include either the direct interaction of PCB sulfates with receptors or their serving as a localized precursor for OH-PCBs. The formation of PCB sulfates is catalyzed by cytosolic sulfotransferases, and, when transported into the serum, these metabolites may be retained, taken up by other tissues, and subjected to hydrolysis catalyzed by intracellular sulfatase(s) to regenerate OH-PCBs. Dynamic cycling between PCB sulfates and OH-PCBs may lead to further metabolic activation of the resulting OH-PCBs. Ultimate toxic endpoints of such processes may include endocrine disruption, neurotoxicities, and many others that are associated with exposures to PCBs and OH-PCBs. This review highlights the current understanding of the complex roles that PCB sulfates can have in the toxicities of PCBs and OH-PCBs and research on the varied mechanisms that control these roles.

Keywords:

• Sulfation
• sulfotransferase
• SULT
• sulfatase
• STS
• endocrine disruption
• neurotoxicity
• polychlorinated biphenyl
• PCB
• OH-PCB
• PCB sulfate
• toxicity
• metabolic activation
• detoxication
• inhibition

Acknowledgments

Where the work of the authors was mentioned in this review, those studies were supported by the National Institute of Environmental Health Sciences, National Institutes of Health, through grants NIH P42 ES013661 and P30 ES005605. The contents of this review are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. Finally, we wish to acknowledge the valuable comments provided by the anonymous external reviewers assigned by the editor.

Declaration of interest

No potential conflict of interest was reported by the author(s).