Of Hydroxylated Polychlorinated Biphenyls Research Articles

Concentration of hydroxylated polychlorinated biphenyls (OH-PCBs) in the blood of Yusho patients in 2010.

Hydroxylated polychlorinated biphenyls (OH-PCBs) are formed as major metabolites of PCBs by cytochrome P450 enzyme-mediated oxidation. It has been reported that their total concentration in serum samples of Yusho patients ranged from 390 to 1300 pg/g. We measured the concentration of OH-PCBs in blood collected from 183 Yusho patients living in Japan in 2010. The major OH-PCB metabolites were 4-OH-CB187 (ND-1300 pg/g-wet), 4-OH-CB146 + 3-OH-CB153 (8.4-1200 pg/g-wet), 4-OH-CB109 (ND-530 pg/g-wet) and 4'-OH-CB172 (ND-380 pg/g-wet). The total OH-PCBs ranged from 36 to 3800 pg/g-wet. A positive relationship between the concentrations of OH-PCBs and PCBs was observed, but no significant relationship between the concentrations of OH-PCBs and PCDD/DFs was observed.

Levels and patterns of hydroxylated polychlorinated biphenyls (OH-PCBs) and their associations with thyroid hormones in hooded seal ( Cystophora cristata) mother–pup pairs

Blood (plasma/serum) samples from 14 adult female and their pups (1–4 days old) captured in the West Ice, east of Greenland were analysed for concentrations of total and free thyroxine and triiodothyronine (TT4, FT4, TT3, FT3), and hydroxylated polychlorinated biphenyls (OH-PCBs). The levels of all thyroid hormones (THs) were significantly higher in pups than in mothers. Sum OH-PCB levels (ΣOH-PCBs: 4-OH-CB107, 3′-OH-CB138, 4-OH-CB146, 4′-OH-CB172, 4-OH-CB187) were significantly higher in mothers (3.98 ± 1.55 pmol/g; 1.40 ± 0.54 ng/g wet weight) as compared to pups (1.95 ± 0.78 pmol/g; 0.68 ± 0.28 ng/g wet weight). Plasma levels of TT4 and FT4 in mothers increased as a function of pup age, as did levels of individual OH-PCBs in both mothers and pups. The pattern of OH-PCBs in the pups was similar to their mothers. We suggest that OH-PCBs found in pups are transferred from their mothers during gestation and that the transfer also continues after parturition via milk. Principal component analysis (PCA) showed that in pups, 4-OH-CB107 and 3′-OH-CB138 were negatively associated with FT4:FT3 and TT3:FT3 ratios, respectively. These relationships were confirmed by partial correlation analysis correcting for pup age. PCA suggested that 4′-OH-CB172 and 4-OH-CB187 were negatively associated with TT3 in mothers. However, this was not confirmed by correlation tests. Although statistical relationships should be interpreted with caution, the study indicates that young developing seals are more sensitive compared to adults with respect to TH-related effects of OH-PCBs.

Characterization and optimization by experimental design of a liquid chromatographic method for the separation of hydroxylated polychlorinated biphenyls on a polar-embedded stationary phase

Traditionally, the determination of hydroxylated polychlorinated biphenyls (OH-PCBs) has been carried out by gas chromatography (GC). However, the gas chromatographic behavior and sensitivity of this type of hydroxylated compounds are not always satisfactory, hence a prior derivatization of the OH-PCBs must be performed. Therefore, the development of liquid chromatographic methods should prove to be a very interesting task aimed at dealing with the instrumental determination of OH-PCBs. Taking into account that octadecylsilane stationary phases are not the most adequate for the separation of isobaric compounds, an amide-type column has been tested. For the development of the method, the Response Surface Methodology was used, based on a Box–Wilson Central Composite experimental design. The initial content of methanol in the mobile phase, the gradient time, and the concentration and the pH value of the buffer were chosen as relevant experimental parameters. A global optimum was obtained by selecting the elution time, the sensitivity and the overall resolution as responses to optimize. The developed method for liquid chromatography presented a very good resolution and sensitivity, and a reasonably short analysis time. In addition, a retention study was conducted in order to survey the different interactions that take place in the separation process, showing that hydrogen bonding is the main interaction between OH-PCBs and the amide-type stationary phase. However, a substantial contribution of dispersion forces was present in methanol contents in the mobile phase below 65%. Besides, the pH value of the mobile phase was found to be the most important parameter to control the hydrogen bond forces and therefore, to regulate the OH-PCBs separation.

Hydroxylated polychlorinated biphenyls (OH-PCBs) induce vitellogenin through estrogenic activity in primary-cultured hepatocytes of the Xenopus laevis

Vitellogenin (VTG)-inducing activities of 21 kinds of hydroxylated polychlorinated biphenyls (OH-PCBs) were investigated by an assay system using the primary-cultured hepatocyte of the adult male Xenopus laevis. An enzyme-linked immunoabsorbent assay (ELISA) was able to detect VTG at a minimum detection limit of 0.2 ng mL −1. The levels of VTG production in hepatocytes of male X. laevis exposed to six kinds of OH-PCB isomers (2′-OH-CB30, 3′-OH-CB30, 4′-OH-CB30, 4′-OH-CB50, 4′-OH-CB61 4′-OH-CB65) were significantly higher as compared to the control group ( p < 0.05). The relative ranking of the OH-PCBs was E2 (100%), 4′-OH-CB30 (2.0%) > 2′-OH-CB30 (0.15%) > 4′-OH-CB61 (0.046%) > 3′-OH-CB30 (0.013%) > 4′-OH-CB50 (0.002%) > 4′-OH-CB65 (0.0001%). Although there were some differences between the estrogenicity values by the VTG-inducing activities and yeast two-hybrid assay for human estrogen receptor α (ERα). The results from VTG-assays suggested that an important factor for determining estrogenicity is the positions of the hydroxyl group and chlorine with the highest activity resulting from a para-hydroxyl group. The OH-PCB structures of high rank order in the VTG-assay had no chlorine substituted phenolic ring. Moreover, the meta-chlorine substituted phenolic ring is an important factor in determining estrogenicity. The OH-PCBs with meta-chlorine substituted phenolic ring did not show estrogenicity during VTG-assay.

Determination and Characterization of Hydroxylated Polychlorinated Biphenyls (OH-PCBs) in Serum and Adipose Tissue of Japanese Women Diagnosed with Breast Cancer

In the present study, we analyze and characterize the levels of PCBs and OH-PCBs in serum and breast adipose tissue, and measure TH (total 3,5,5'-triiodothyronine (tT3) and total l-thyroxine (tT4)) levels in serum of Japanese women diagnosed with breast cancer (n = 51) to know how PCBs affect thyroid hormone homeostasis. Concentrations of Sigma(90)OH-PCBs in serum and adipose tissues were 630 pg g(-1) serum wet wt. and 140 pg/ g(-1) lipid wt., respectively, and the levels of OH-PCBs in adipose tissues were 4-5 times lower than in serum. The tT3 and tT4 concentrations in serum (n = 20) were 1.3 ng g(-1) serum wet wt. and 62 ng g(-1) serum wet wt., respectively. Among all the OH-PCBs, 4'-OH-CB101/120, 4-OH-CB107/4'-OH-CB108, 3'-OH-CB138, 4-OH-CB146, 3-OH-CB153, 4'-OH-CB172, and 4-OH-CB187 were the dominant isomers in serum. No significant correlation between the concentrations of the TH and OH-PCBs in serum was observed (p > 0.05). The results indicated that the relationship between the OH-PCB levels and the thyroid hormone markers was rare. From analysis of two kinds of human biological samples, it was estimated that OH-PCBs have little effect on thyroid hormone homeostasis.

Detection of Hydroxylated Polychlorinated Biphenyls (OH-PCBs) in the Abiotic Environment: Surface Water and Precipitation from Ontario, Canada

Hydroxylated PCBs (OH-PCBs) are well-known metabolites of PCBs in organisms, but there has been no direct study of their presence in the abiotic environment. In this study, OH-PCBs were determined in samples of rain, snow, and surface waters from sites in Ontario, Canada. OH-PCBs were quantified by gas chromatography with high-resolution mass spectrometry (GC-HRMS)in order to provide complete characterization of all OH-PCB homolog groups. OH-PCBs and PCBs were detected in all the samples analyzed, although half of the sigmaOH-PCBs could not be identified even with 71 individual congener standards. Total concentrations of OH-PCBs (sigmaOH-PCBs) in water ranged from 0.87 to 130 pg/L and from 230 to 990 pg/g in particulate organic matter. Total fluxes of those compounds in snow and rain were from < 1 to 100 pg/m2 and from < 1 to 44 pg/ m2/day, respectively. Higher sigmaOH-PCB fluxes in rain were found in southern Ontario than in a remote north-central Ontario site possibly reflecting greater sources of precursor PCBs near urban areas. Relatively higher sigmaOH-PCB concentrations were found in surface waters from sites near sewage treatment plant (STP) outfalls in the cities of Toronto (130 pg/L) and Hamilton (35 pg/L) than in offshore samples from Lake Ontario (1.6 pg/L). The results indicate that STPs are one of the sources of OH-PCBs for lake waters in this region. Similar homolog and congener profiles in rain and offshore surface water samples suggest that atmospheric deposition is the predominant source at offshore sites. This is the first report to detect the OH-PCBs in the abiotic environment.

Quantitative structure–activity relationships for prediction of the toxicity of hydroxylated and quinoid PCB metabolites

Quantitative structure-activity relationship (QSAR) models were developed for the in vitro potencies to downregulate gap junctional intercellular communication (GJIC) of hydroxylated polychlorinated biphenyls (OH-PCBs) and PCB quinines using partial least squares (PLS) regression. Quantum chemical descriptors computed by the semiempirical AM1, PM3 and MNDO methods were used as predictor variables. The cross-validated Q2cum values for the three optimal QSAR models are 0.784, 0.789 and 0.755, respectively, indicating good predictive capabilities for the acute inhibition of GJIC (IC(50)) of oxygenated PCB derivatives. The slightly higher Q2cum value of the model using computed molecular descriptors from the PM3 Hamiltonian suggested a slightly better predictive power than the models developed using AM1 or MNDO. However, given these dispersion parameters in these three optimal models, there would not be a significant difference between the Q2cum values. Results from this study showed that the logarithmic scale of IC(50) is affected by different molecular structural descriptors.

Docking and QSAR studies of an indirect estrogenic effect of hydroxylated PCBs

A quantitative structure-activity relationship (QSAR) of hydroxylated polychlorinated biphenyls (OH-PCBs) potency to inhibit human estrogen sulfotransferase (hEST), was modeled using multivariate methods and calculated semi-empirical descriptors. The QSAR model included 10 selected OH-PCBs, recently reported experimental inhibition potencies of hEST and 17 physico- chemical parameters. The cross-validated explained variance of 0.71 indicates a high predictive capacity of the model. The most important parameters were sub-molecular electronic parameters, such as partial atomic charges and nucleophilic electron densities. The natural substrate estradiol and OH-PCBs have been suggested to inhibit hEST by non-competitive binding to a not yet identified allosteric site. Potential allosteric binding sites in the crystal structure of mouse estrogen sulfotransferase (mEST) and in a homology model of hEST were investigated and discussed using the programs CAST and GRAMM. In general, the most abundant docking sites using GRAMM were in agreement with pockets defined by CAST. These preliminary results should be verified and more detailed studies undertaken when the active dimer of hEST is available. The results indicate that other similar pollutants may well interfere with the sulfonation of estradiol.

Hydroxylated PCB metabolites and PCBs in serum from pregnant Faroese women.

In the Faroe Islands in the North Atlantic, the traditional diet includes pilot whale meat and blubber and other marine food. Fatty fish and blubber of mammals may contain high concentrations of organohalogen substances (OHSs). Elevated levels of OHSs have been reported from the Faroe Islands, first documented in breast milk samples obtained in 1987. The aim of this study was to determine the concentrations of hydroxylated polychlorinated biphenyls (OH-PCBs) and polychlorinated biphenyls (PCBs) in serum samples from pregnant Faroese women known to differ in their dietary habits. High concentrations of OH-PCBs and PCBs were found in part of the human serum samples analyzed, and the relative OH-PCB and PCB congener distributions were similar to those observed elsewhere. There was a wide span between the lowest and highest OH-PCB and PCB concentrations in the serum samples analyzed, with ranges of 19-1,800 ng/g lipid weight (lw) and 150-22,000 ng/g lw, respectively. The ratio of sigmaOH-PCB/sigmaPCB averaged about 10% and varied little. 4-Hydroxy-2,2,3,4,5,5,6-heptachlorobiphenyl was the most abundant OH-PCB metabolite in all samples analyzed, with four other OH-PCB congeners as dominating metabolites in the serum. More than 25 additional OH-PCBs were indicated. This study confirms the presence of high concentrations of organohalogen substances in populations or areas far removed from their sources.

Hydroxylated polychlorinated biphenyls as inhibitors of the sulfation and glucuronidation of 3-hydroxy-benzo[a]pyrene.

Polychlorinated biphenyls (PCBs) can be metabolized by cytochromes P450 to hydroxylated biotransformation products. In mammalian studies, some of the hydroxylated products have been shown to be strong inhibitors of steroid sulfotransferases. As a part of ongoing research into the bioavailability of environmental pollutants in catfish intestine, we investigated the effects of a series of hydroxylated PCBs (OH-PCBs) on two conjugating enzymes, phenol-type sulfotransferase and glucuronosyltransferase. We incubated cytosolic and microsomal samples prepared from intestinal mucosa with 3-hydroxy-benzo[a]pyrene and appropriate cosubstrates and measured the effect of OH-PCBs on the formation of BaP-3-glucuronide and BaP-3-sulfate. We used PCBs with 4, 5, and 6 chlorine substitutions and the phenolic group in the ortho, meta, and para positions. OH-PCBs with the phenolic group in the ortho position were weak inhibitors of sulfotransferase; the median inhibitory concentration (IC50) ranged from 330 to 526 microM. When the phenol group was in the meta or para position, the IC50 was much lower (17.8-44.3 microM). The OH-PCBs were more potent inhibitors of glucuronosyltransferase, with IC50s ranging from 1.2 to 36.4 microM. The position of the phenolic group was not related to the inhibitory potency: the two weakest inhibitors of sulfotransferase, with the phenolic group in the ortho position, were 100 times more potent as inhibitors of glucuronosyltransferase. Inhibition of glucuronosyltransferase by low concentrations of OH-PCBs has not been reported before and may have important consequences for the bioavailability, bioaccumulation, and toxicity of other phenolic environmental contaminants.

Properties, Production, and Uses

The detoxification and degradation of polychlorinated biphenyls (PCBs) have been studied. However, little information is available about the biological mechanisms involved in the metabolism of hydroxylated polychlorinated biphenyls (OH-PCBs) and methoxylated polychlorinated biphenyls (MeO-PCBs) by specific microorganism. In this study, the simultaneous formation of OH-PCB (major metabolite) and MeO-PCB (minor metabolite) was found in Bacillus subtilis after exposure to PCB. Interconversion between MeO-PCB and OH-PCB was also observed and the demethylation ratio of MeO-PCB was higher than the methylation ratio of OH-PCB. The high-throughput RNA-sequencing (RNA-Seq) was conducted to analyze the genes involved in the metabolism processes. The potential metabolism pathways of PCB by Bacillus subtilis were proposed. PCB can be transformed to OH-PCB by Cytochrome P450 encoded by the genes bioI and cypA. The genes ycgJ and ycgI that are related with methyltransferase are potentially involved in the subsequent biotransformation from OH-PCB to MeO-PCB. MeO-PCB was prone to be transformed to OH-PCB by a group of hydrolases. This is the first study considering the mechanism involved in the interconversion between OH-PCBs and MeO-PCBs by microorganism. These findings broaden our insights into the biotransformation mechanism of PCBs in the environment.