Xenobiotic Activities in Serum of Inuit and European Populations: Effects on Semen DNA Quality Markers

Human exposure to environmental contaminants is ubiquitous and can affect individuals living close to as well as remote from the sources of contaminants. Persistent organic pollutants (POPs) include polychlorinated dibenzo-p-dioxins/furans (PCDDs/PCDFs), polychlorinated biphenyls (PCBs) and certain pesticide residues. Exposure to POPs elicits a number of species- and tissue-specific toxic responses including effects on the reproductive-, immune- and thyroid system. Adverse effects have been documented in wildlife populations, whereas no clear cut evidence for adverse endocrine-related human health effects has been obtained. The toxicological assessment of individuals is complicated by the life long exposure to a complex mixture of contaminants. The present study compare the actual serum level of xeno-hormone (estrogenic and androgenic) and dioxin-like activity between populations from Greenland (Inuit's) and Europe (Sweden, Poland, Ukraine) for finally to evaluate possible associations to the POP markers PCB153 and p,p'-DDE, semen DNA quality markers and lifestyle parameters.The SPE-HPLC serum fraction containing the actual mixture of bio-accumulated POPs, free of endogenous hormones, was used to determine the effect on the estrogen- (ER) and androgen-receptor (AR) trans-activity in stable transfected ER-luc MVLN and transient transfected ARE-luc CHO-K1 cells, respectively. Serum dioxin-like activity was determined in serum fat extracts using the stable AhR-luc transfected Hepa 1.12cR cells. Sperm DNA damage was measured using Terminal Deoxynucleotydil Transferase assay and apoptotic markers Fas and Bcl-xL were determined by immune methods. Fluoremetric sperm chromatin structure assay was used to assess sperm DNA/chromatin integrity (DFI).The integrated net xenobiotic activities determined in serum elicited a district dependent pattern. Compared to controls significantly effects of the actual serum POP fraction on the activity of each of the receptors (ER, AR and AhR) was observed. Inuit's differed from the European groups by a higher frequency of samples with antagonized ER, higher AR potency and lower dioxin-like activity. Multiple regressions showed an interaction between semen DNA quality markers (DFI, DNA damage) and xenoestrogenic and dioxin-like activity across the groups. In the separate study groups Inuit's showed a negative correlation between the DNA quality markers and ER and AhR activities and no or few positive correlations for the European samples. No consistent association to the two POP markers was found.The data suggested that different POP burden profiles elicit differences in net xenobiotic receptor activities and effects on semen DNA quality markers. The Inuit's in general differed from the European groups. Future studies might elucidate whether genetic and/or life style factors play a role in the observed differences.