Impact of polychlorinated biphenyls contamination on estrogenic activity in human male serum

Abstract

Polychlorinated biphenyls (PCBs) are thought to cause numerous adverse health effects, but their impact on estrogen signaling is still not fully understood. In the present study, we used the ER-CALUX bioassay to determine estrogenic/antiestrogenic activities of the prevalent PCB congeners and PCB mixtures isolated from human male serum. The samples were collected from residents of an area with an extensive environmental contamination from a former PCB production site as well as from a neighboring background region in eastern Slovakia. We found that the lower-chlorinated PCBs were estrogenic, whereas the prevalent higher-chlorinated PCB congeners 138, 153, 170, 180, 187, 194, 199, and 203, as well as major PCB metabolites, behaved as antiestrogens. Coplanar PCBs had no direct effect on estrogen receptor (ER) activation in this in vitro model. In human male serum samples, high levels of PCBs were associated with a decreased ER-mediated activity and an increased dioxin-like activity, as determined by the DR-CALUX assay. 17beta-Estradiol (E2) was responsible for a major part of estrogenic activity identified in total serum extracts. Significant negative correlations were found between dioxin-like activity, as well as mRNA levels of cytochromes P450 1A1 and 1B1 in lymphocytes, and total estrogenic activity. For sample fractions containing only persistent organic pollutants (POPs), the increased frequency of antiestrogenic samples was associated with a higher sum of PCBs. This suggests that the prevalent non-dioxin-like PCBs were responsible for the weak antiestrogenic activity of some POPs fractions. Our data also suggest that it might be important to pay attention to direct effects of PCBs on steroid hormone levels in heavily exposed subjects.

Figure 1

Chemical structures of selected PCB congeners examined for the antiestrogenic/estrogenic activities in human breast carcinoma T47D.Luc cells (ER-CALUX assay). (A) Lower molecular-weight PCBs present in low concentrations in male blood samples. (B) Non-ortho-chlorinated PCB. (C) PCB congeners occurring in relatively higher concentrations in male blood. (D) Prevalent high-molecular-weight PCB congeners.

Figure 2

Dose-dependent estrogenic effect of the individual PCB congeners (A) and the combined effect of two estrogenic PCB congeners (PCBs 28 and 52) plus 3 pM E₂ (B) on induction of luciferase activity in the ER-CALUX assay. Results are expressed as mean ± SD. *p < 0.05, and **p < 0.01 compared with control.

Figure 3

Dose-dependent effect of four indicator PCB congeners (A) and six higher chlorinated PCBs (B) on 3 pM E₂-induced luciferase activity in T47D.Luc cells. Results are expressed as mean ± SD.

Figure 4

Antiestrogenic potencies of PCB 153 and an artificial mixture of the most prevalent PCBs (ratio of 6:3:5:2 of PCBs 153, 138, 170, and 180). Results are expressed as mean ± SD. ^*p < 0.05 compared with an equimolar concentration of PCB 153.

Figure 5

Estrogenic activities (A) and dioxin-like activities (B) of extracts of human male serum samples. Median values of quartiles were stratified according to PCB concentrations. *Significantly different from groups with lower PCB levels (p = 0.02; Mann-Whitney U test); concentrations of PCBs (μg/mL serum) are as follows: first quartile, 0.0020–0.0055; second quartile, 0.0055–0.0078; third quartile, 0.0079–0.0138; fourth quartile, 0.0139–0.1755.

Figure 6

Principal component analysis of the measured parameters of the serum samples. Abbreviations: Fraction (ER), number of estrogenic samples of the fraction of POPs; fraction (anti-ER), number of anti-estrogenic samples of the fraction of POPs; ∑PCBs, serum of 17 PCB congeners.

Figure 7

Potential mechanisms of antiestrogenic effects of coplanar and noncoplanar PCBs.