Persistent Organic Pollutants: Biomonitoring and Hormone-Disrupting Effect Biomarkers

What is it about?

This MiniReview gives a short overview of an update on exposure and endocrine-disrupting effect biomarkers of persistent organic pollutants (POPs) in vitro and ex vivo. Humans are exposed to complex mixtures of chemicals, which have individually different biological potentials and effects. Therefore, the assessment of the combined, integrated biological effect of the actual chemical mixture in human body is important. POPs include lipophilic legacy POPs such as polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins/furans (PCDDs/PCDFs), organochlorine pesticides (OCPs) and polybrominated flame-retardants and the amphiphilic perfluorinated alkyl acids (PFAAs). They are persistent in the environment and biomagnifies through the food web and bio-accumulate in humans and animals. Studies have shown that POPs are potential endocrine disrupters via affecting the function of hormone receptors such as estrogen (ER), androgen (AR), thyroid (TH) and aryl hydrocarbon receptor (AhR). We have for the very first time developed methods for extraction of legacy POPs and PFAAs from human serum with simultaneous removal of endogenous sex hormones followed by the determination of the combined effect on xenohormone receptors (ER and AR) and Ah-receptor function. Biomonitoring studies showed that the Arctic population such as Greenlandic Inuit have higher body burden of lipophilic legacy POPs than Europeans. The exposure levels and profiles differs among the various Greenlandic districts and gender. The profile of ex vivo combined effect biomarkers measured as the xenohormone receptor and AhR function of the complex serum mixture of legacy POPs reflected the differences in exposure biomarkers. The body levels of PFASs in human vary worldwide, with American population being slightly higher than European, Asian and Australian populations. We found that the actual combined mixture of serum PFAAs had the potential to induce ER transactivation and further increase the ER ligand 17β estradiol-induced ER transactivity. Thus, the PFAAs at levels found in human serum – may play a role in endocrine disruption via the ER. Studies have shown some POPs possess the carcinogenic potentials. In vitro studies showed that some of the PFAAs have the potential to induce oxidative stress in terms of reactive oxygen species (ROS) production and DNA damage in the cell line representing the human liver. We found that serum levels of POPs, especially PFAAs might be risk factors in the development of breast cancer in Inuit, and hormone disruption, as shown by the combined serum legacy POP-related xenohormone receptor transactivities, may play a role in the development of breast cancer. Furthermore, our studies showed that genetic polymorphisms in the cytochrome P450 enzyme differed significantly between Greenlandic Inuit and Europeans. Therefore, xenohormone receptor transactivities can be used as an ex vivo integrated biomarker of POP exposure and effects. Biomonitoring studies on serum POP exposures and biomarkers of effects ex vivo of the combined serum POP mixture have the potential to elucidate the relationship between emissions, exposure, biological effects and health risks. Determination of relevant genetic polymorphisms might help to assess the health risk of an individual upon exposure to POPs. Further epidemiological molecular-genetic studies are warranted to document the effect.

Featured Image

Why is it important?

This MiniReview gives a short overview of an update on exposure and endocrine-disrupting effect biomarkers of persistent organic pollutants (POPs) in vitro and ex vivo. Humans are exposed to complex mixtures of chemicals, which have individually different biological potentials and effects. Therefore, the assessment of the combined, integrated biological effect of the actual chemical mixture in human body is important. We have for the very first time developed methods for extraction of legacy POPs and PFAAs from human serum with simultaneous removal of endogenous sex hormones followed by the determination of the combined effect on xenohormone receptors (ER and AR) and Ah-receptor function.

Perspectives