The microbial degradation of halogenated diaryl ethers

The structurally related polyhalogenated diaryl ethers such as diphenyl ethers (DEs), dibenzofurans (DFs), and dibenzo-p-dioxins (DDs) are regarded, due to their physicochemical and toxicological properties, as a class of compounds giving reason for serious environmental concern. While the nonhalogenated basic structures are biodegradable under aerobic conditions, there is the need for rather specialized strains to mineralize the halogenated derivatives. Certain halogenated metabolites might cause serious problems such as having inhibitory effects upon the degradation. Anaerobic methanogenic consortia do have the ability to almost completely dehalogenate even polyhalogenated congeners. It has been shown that certain fungi are capable of transforming chlorinated DFs and DDs by the activity of nonspecific enzymes such as lignin-peroxidases.     

Computational identification and analysis of functional polymorphisms involved in the activation and detoxification genes implicated in endometriosis

Endometriosis is a complex disorder of the female reproductive system where endometrial tissue embeds and grows at extrauterine location leading to inflammation and pain. Hundreds of polymorphisms in several genes have been studied as probable risk factors of this debilitating disease. Bioinformatics tools have come a long way in augmenting the search for putative functional polymorphisms in human diseases. In this study we have explored 16 genes involved in the detoxification of xenobiotic chemicals that are implicated in endometriosis by utilising publically available programs like SIFT, Polyphen, Panther, FastSNP, SNPeffect and PhosSNP. The variations among different ethnic populations of the SNPs were studied. We then calculated the extent to which bioinformatics based predictions are concurrent with real world epidemiological, genotyping studies using a set of SNPs that have been studied in endometriosis case–control studies. Our study shows that there is a significant positive correlation (r = 0.569, p < 0.005) between the summary of the predicted scores taken from 4 different servers and the odds ratio found from epidemiological studies. This report has identified and catalogued various deleterious SNPs that could be important in endometriosis and could aid in further analysis by in vitro and in vivo methods for the better understanding of the disease pathophysiology.     

美国威斯康星州的Lower Fox River和Lower Green Bay水域的污染沉积物对鱼类影响的研究

LowerFoxRiver和LowerGreenBy水域的沉积物造成了该地区的轻度污染。经测定和分析,沉积物中含有较高的PCBs和较低含量的PCDFs及PCDDs,在鱼样品中呈现有PCBs和农药。组织病理学检查,鱼体内寄生虫感染发生率较高,部分肝组织坏死,出现肉芽瘤状物,胰腺纤维化,但没有发现鱼体上有肿瘤。     

First Evidence for Homologous Recombination-mediated Large DNA Inversion on the Bacillus subtilis 168 Chromosome

A Bacillus subtilis 168 strain carrying an inversion of about 1600kb-long chromosomal DNA was isolated. Physical and genetic analyses demonstrated that the inversion was generated as a result of homologous recombination between two homologous sequences integrated at the met and leuB loci. This is the first clear evidence of a large stable chromosomal inversion induced by homologous recombination in B. subtilis.     

Toxicological biomarkers of 2,3,4,7,8-pentachlorodibenzofuran in proteins secreted by HepG2 cells

Using a proteomic approach, a study was conducted for determination of the effects of 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PCDF) on proteins secreted by HepG2 cells. Briefly, HepG2 cells were exposed to various concentrations of 2,3,4,7,8-PCDF for 24 or 48 h. MTT and comet assays were then conducted for determination of cytotoxicity and genotoxicity, respectively. Results of an MTT assay showed that 1 nM of 2,3,4,7,8-PCDF was the maximum concentration that did not cause cell death. In addition, a dose- and time dependent increase of DNA damage was observed in HepG2 cells exposed to 2,3,4,7,8-PCDF. Therefore, two different concentrations of 2,3,4,7,8-PCDF, 1 and 5 nM, were selected for further analysis of proteomic biomarkers using two different pI ranges (4-7 and 6-9) and large two dimensional gel electrophoresis. Results showed identification of 32 proteins ( 29 up- and 3 down-regulated) by nano-LC-ESI-MS/MS and nano-ESI on a Q-TOF2 MS. Among these, the identities of pyridoxine-5'-phosphate oxidase, UDP-glucose 6-dehydrogenase, plasminogen activator inhibitor I precursor, plasminogen activator inhibitor-3, proteasome activator complex subunit 1, isoform 1 of 14-3-3 protein sigma, peptidyl-prolyl cis-trans isomerase A, 14-3-3 protein gamma, protein DJ-1, and nucleoside diphosphate kinase A were confirmed by western blot analysis. The differential expression of protein DJ-1, proteasome activator complex subunit 1 and plasminogen activator inhibitor-3 was further validated in plasma proteins from rats exposed to 2,3,4,7,8-PCDF. These proteins could be used as potential toxicological biomarkers of 2,3,4,7,8-PCDF.     

The immunotoxic effects of dual exposure to PCP and TCDD

Pentachlorophenol (PCP) was a commonly used fungicide, herbicide, insecticide, and bactericide in industrial, agricultural, and domestic settings; however, it was also contaminated with polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). It has been reported that technical grade PCP had immunosuppressive effects and that the immune system was the major target of PCDD/PCDFs toxicity. Although the immune response after exposure to PCP or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been studied, the toxic effects of exposure to both PCP and TCDD have not yet been reported. The aim of this study was to evaluate the effects on immune cells from mice intraperitoneally immunized with OVA and subsequently treated with PCP or TCDD alone or in combination by gavage. The animals were terminated on day 7 and 14, and the spleen and plasma samples were collected for immunotoxicity evaluation. The numbers and populations of splenocytes, T cell-derived cytokines produced by splenocytes, splenocyte-generated cytotoxicity and OVA-specific antibodies in plasma were investigated. Our results indicate that the spleen/body weight ratio and splenocyte number was reduced by TCDD alone; in addition, this reduction was enhanced when TCDD was combined with PCP. Exposure to TCDD alone or in conjunction with PCP suppressed many ovalbumin (OVA)-stimulated cytokines, including IL-2, IFN-γ, IL-4, IL-5, and IL-10. Furthermore, the immunoglobulins IgG and IgM were suppressed in mice administered by PCP alone, but the suppressive effects were greater in mice treated with TCDD alone or in combination with PCP. Co-exposure to PCP and TCDD resulted in an antagonistic effect on TCDD-induced suppression of IFN-γ and IL-10. Our results demonstrate that PCP alone is immunotoxic, regardless of the presence of TCDD. PCP led to mild changes in cytokine secretion, and it compromised splenocyte-generated cytotoxicity and IgM and IgG antibody production on day 7. The finding that PCP antagonizes TCDD-induced IFN-γ suppression could be due to the competitive binding of PCP to AhR (aryl hydrocarbon receptor).     

Comparative kinetic study of the binding between 2,3,7,8-tetrachlorodibenzo-ρ-dioxin and related ligands with the hepatic Ah receptors from several rodent species

Kinetic analysis of the time course of association of [³H]-2,3,7,8-tetrachlorodibenzo-ρ-dioxin with hepatic cytosoi from five rodent species gave additional evidence for differences in the properties of the Ah receptor ligand binding subunit between species. A parallel study of the association of six tritiated polychlorinated dibenzopρ-dioxins and dibenzofurans with hepatic Ah receptor from Wistar rat and C57BL/6 mouse showed that their rank order for kinetic affinity did not correlate with the rank ordering of their toxic potency- and may vary according to the source of the Ah receptor.     

Sorption/Desorption of Polychlorinated Dibenzo-P-Dioxins and Polychlorinated Dibenzo Furans (PCDDs/PCDFs) in the Presence of Cyclodextrins

The goal of this study was to investigate the usefulness of cyclodextrins (CDs) for the removal of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo furans (PCDDs/PCDFs) in soil and water. Five CDs having different molecular cavities and active functional groups were selected and evaluated for their ability to include (trap) PCDDs/PCDFs in soil and water. For the soil experiments, CDs were added to the soil on day one and the concentrations of unbound PCDDs/PCDFs were monitored over a 28-day period. Parallel control experiments were conducted to assist in the process performance evaluation. The ability of CDs to remove PCDDs/PCDFs from the contaminated soil was dependent upon the type of CD used and constituents of PCDDs/PCDFs. Among the five CDs investigated, hydroxypropyl-β -cyclodextrin (HPBCD) gave the highest removal efficiency for all components of PCDDs/PCDFs. The removal efficiency of total PCDDs/PCDFs was 81% one day after application of CDs and then increased to 96% after 28 days. The α -cyclodextrin (ACD) and β -cyclodextrin (BCD) removed only 45% and 50% of the total PCDDs/PCDFs after 28 days, respectively, whereas hydroxypropyl-γ -cyclodextrin (HPGCD) removed 80% of the total PCDDs/PCDFs.