Kegg Pathway: Biphenyl degradation

Sci Total Environ. 2009 Nov 10;
Letcher RJ, Bustnes JO, Dietz R, Jenssen BM, Jørgensen EH, Sonne C, Verreault J, Vijayan MM, Gabrielsen GW

Persistent organic pollutants (POPs) encompass an array of anthropogenic organic and elemental substances and their degradation and metabolic byproducts that have been found in the tissues of exposed animals, especially POPs categorized as organohalogen contaminants (OHCs). OHCs have been of concern in the circumpolar arctic for decades. For example, as a consequence of bioaccumulation and in some cases biomagnification of legacy (e.g., chlorinated PCBs, DDTs and CHLs) and emerging (e.g., brominated flame retardants (BFRs) and in particular polybrominated diphenyl ethers (PBDEs) and perfluorinated compounds (PFCs) including perfluorooctane sulfonate (PFOS) and perfluorooctanic acid (PFOA) found in Arctic biota and humans. Of high concern are the potential biological effects of these contaminants in exposed Arctic wildlife and fish. As concluded in the last review in 2004 for the Arctic Monitoring and Assessment Program (AMAP) on the effects of POPs in Arctic wildlife, prior to 1997, biological effects data were minimal and insufficient at any level of biological organization. The present review summarizes recent studies on biological effects in relation to OHC exposure, and attempts to assess known tissue/body compartment concentration data in the context of possible threshold levels of effects to evaluate the risks. This review concentrates mainly on post-2002, new OHC effects data in Arctic wildlife and fish, and is largely based on recently available effects data for populations of several top trophic level species, including seabirds (e.g., glaucous gull (Larus hyperboreus)), polar bears (Ursus maritimus), polar (Arctic) fox (Vulpes lagopus), and Arctic charr (Salvelinus alpinus), as well as semi-captive studies on sled dogs (Canis familiaris). Regardless, there remains a dearth of data on true contaminant exposure, cause-effect relationships with respect to these contaminant exposures in Arctic wildlife and fish. Indications of exposure effects are largely based on correlations between biomarker endpoints (e.g., biochemical processes related to the immune and endocrine system, pathological changes in tissues and reproduction and development) and tissue residue levels of OHCs (e.g., PCBs, DDTs, CHLs, PBDEs and in a few cases perfluorinated carboxylic acids (PFCAs) and perfluorinated sulfonates (PFSAs)). Some exceptions include semi-field studies on comparative contaminant effects of control and exposed cohorts of captive Greenland sled dogs, and performance studies mimicking environmentally relevant PCB concentrations in Arctic charr. Recent tissue concentrations in several arctic marine mammal species and populations exceed a general threshold level of concern of 1part-per-million (ppm), but a clear evidence of a POP/OHC-related stress in these populations remains to be confirmed. There remains minimal evidence that OHCs are having widespread effects on the health of Arctic organisms, with the possible exception of East Greenland and Svalbard polar bears and Svalbard glaucous gulls. However, the true (if any real) effects of POPs in Arctic wildlife have to be put into the context of other environmental, ecological and physiological stressors (both anthropogenic and natural) that render an overall complex picture. For instance, seasonal changes in food intake and corresponding cycles of fattening and emaciation seen in Arctic animals can modify contaminant tissue distribution and toxicokinetics (contaminant deposition, metabolism and depuration). Also, other factors, including impact of climate change (seasonal ice and temperature changes, and connection to food web changes, nutrition, etc. in exposed biota), disease, species invasion and the connection to disease resistance will impact toxicant exposure. Overall, further research and better understanding of POP/OHC impact on animal performance in Arctic biota are recommended. Regardless, it could be argued that Arctic wildlife and fish at the highest potential risk of POP/OHC exposure and mediated effects are East Greenland, Svalbard and (West and South) Hudson Bay polar bears, Alaskan and Northern Norway killer whales, several species of gulls and other seabirds from the Svalbard area, Northern Norway, East Greenland, the Kara Sea and/or the Canadian central high Arctic, East Greenland ringed seal and a few populations of Arctic charr and Greenland shark.

Int J Biol Macromol. 2009 Oct 30;
Baig MS, Manickam N

Biphenyl dioxygenase is a microbial enzyme which catalyzes the stereospecific dioxygenation of aromatic rings of Biphenyl congeners leading to their degradation. Hence, it has attracted the attention of researchers due to its ability to oxidize chlorinated Biphenyls, which are one of the serious environmental contaminants. In the present study, the three-dimensional model of alpha-subunit of Biphenyl dioxygenase (BphA) from Comamonas testosteroni B-356 has been constructed. The resulting model was further validated and used for docking studies with a class of chlorinated Biphenyls such as Biphenyl,3,3'-dichloroBiphenyl and 4,4'-dichloroBiphenyl. The kinetic parameters of these Biphenyl compounds were well matched with the docking results in terms of conformational and distance constraints. The binding properties of these Biphenyl compounds along with identification of critical active site residues could be used for further site-directed mutagenesis experiments in order to identify their role in activity and substrate specificity, ultimately leading to improved mutants for degradation of these toxic compounds.

Food Chem Toxicol. 2009 Oct 29;
Abdalla FH, Bellé LP, De Bona KS, Bitencourt PE, Pigatto AS, Moretto MB

Adenosine deaminase (ADA) is involved in purine metabolism and plays a significant role in the immune system. The focus of this investigation was to examine the effects of low concentrations of organic mercury on ADA activity in human leukocytes and to investigate the relationship between these effects and cell death. We have examined the protective potential effects of Allium sativum extract (GaE) against Methylmercury (MeHg)-induced cytotoxic effects on human leucocytes under in vitro conditions. MeHg (0.05-10muM) significantly decreased leukocyte viability (58.97% for MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) and 51.67% for Alamar Blue (AB) and this decrease was positively correlated to the MeHg-induced inhibition of ADA activity. N-acetylcysteine (NAC) and GaE prevented both the MeHg-induced cytotoxic effects on leukocytes according to MTT and AB assays and the effects on the ADA activity. The present results suggest that the protective effects of GaE against MeHg-induced leukocyte damage is related to the removal of oxidant species generated in the presence of MeHg due to the antioxidant efficacy of garlic constituents. It is important to point out that the intense presence of ADA in Leukocyte suspension (LS) highlights the relevant effects in the immune system and in vitro cytotoxicity of MeHg exposure.

J Biol Chem. 2009 Oct 29;
Lack NA, Yam KC, Lowe ED, Horsman GP, Owen RL, Sim E, Eltis LD

In the recently identified cholesterol catabolic pathway of Mycobacterium tuberculosis, HsaD is proposed to catalyze the hydrolysis of a C-C bond in 4,5-9,10-diseco-3-hydroxy-5,9,17-tri-oxoandrosta-1(10),2-diene-4-oic acid (DSHA), the cholesterol meta-cleavage product (MCP), and has been implicated in the intracellular survival of the pathogen. Herein, purified HsaD demonstrated 4 to 33 times higher specificity for DSHA (k(cat)/K(m) = 3.3 +/- 0.3 x 10(4) M(-1)s(-1)) than for the Biphenyl metabolite HOPDA (2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid) and a synthetic analogue, HOPODA (8-(2-chlorophenyl)-2-hydroxy-5-methyl-6-oxoocta-2,4-dienoic acid), respectively. The S114A variant of HsaD, in which the active site serine was substituted with alanine, was catalytically impaired and bound DSHA with a K(d) of 51 +/- 2 microM. Moreover, the S114A:DSHA species absorbed maximally at 456 nm, 60 nm red-shifted versus the free DSHA enolate. Crystallographic data of the variant in complex with each of HOPDA, HOPODA or DSHA to 1.8-1.9 A indicate that this shift is due to enzyme-induced strain of the enolate. These data indicate that the catalytic serine catalyzes tautomerization. A second role for this residue is suggested by a structural conserved solvent molecule whose position is consistent with it being activated by the serine for nucleophilic attack of the substrate. Finally, part of the alpha-helical lid covering HsaD's active site displayed a ligand-dependent conformational change involving differences in sidechain carbon positions of up to 6.7 A, supporting a previously proposed two-conformation enzymatic mechanism. Overall, these results provide novel insights into the determinants of specificity in a mycobacterial cholesterol-degrading enzyme as well as into the mechanism of MCP hydrolases.

J Mol Cell Cardiol. 2009 Oct 24;
Haim TE, Wang W, Flagg TP, Tones MA, Bahinski A, Numann RE, Nichols CG, Nerbonne JM

There is considerable evidence to support a role for lipotoxicity in the development of diabetic cardiomyopathy, although the molecular links between enhanced saturated fatty acid uptake/metabolism and impaired cardiac function are poorly understood. In the present study, the effects of acute exposure to the saturated fatty acid, palmitate, on myocardial contractility and excitability were examined directly. Exposure of isolated (adult mouse) ventricular myocytes to palmitate, complexed to bovine serum albumin (palmitate:BSA) as in blood, rapidly reduced (by 54+/-4%) mean (+/-SEM) unloaded fractional cell shortening. The amplitudes of intracellular Ca(2+) transients decreased in parallel. Current-clamp recordings revealed that exposure to palmitate:BSA markedly shortened action potential durations at 20%, 50%, and 90% repolarization. These effects were reversible and were occluded when the K(+) in the recording pipettes was replaced with Cs(+), suggesting a direct effect on repolarizing K(+) currents. Indeed, voltage-clamp recordings revealed that palmitate:BSA reversibly and selectively increased peak outward voltage-gated K(+) (Kv) current amplitudes by 20+/-2%, whereas inwardly rectifying K(+) (Kir) currents and voltage-gated Ca(2+) currents were unaffected. Further analyses revealed that the individual Kv current components I(to,f), I(K,slow) and I(ss), were all increased (by 12+/-2%, 37+/-4%, and 34+/-4%, respectively) in cells exposed to palmitate:BSA. Consistent with effects on both components of I(K,slow) (I(K,slow1) and I(K,slow)(2)) the magnitude of the palmitate-induced increase was attenuated in ventricular myocytes isolated from animals in which the Kv1.5 (I(K,slow)(1)) or the Kv2.1 (I(K,slow)(2)) locus was disrupted and I(K,slow)(1) or I(K,slow2) is eliminated. Both the enhancement of I(K,slow) and the negative inotropic effect of palmitate:BSA were reduced in the presence of the Kv1.5 selective channel blocker, diphenyl phosphine oxide-1 (DPO-1).Taken together, these results suggest that elevations in circulating saturated free fatty acids, as occurs in diabetes, can directly augment repolarizing myocardial Kv currents and impair excitation-contraction coupling.

Environ Sci Technol. 2009 Oct 1; 43(19): 7536-42
Wan Y, Wiseman S, Chang H, Zhang X, Jones PD, Hecker M, Kannan K, Tanabe S, Hu J, Lam MH, Giesy JP

Polybrominated diphenyl ethers (PBDEs) have been widely used as flame retardants. The structurally related hydroxylated PBDEs (OH-PBDEs) and methoxylated PBDEs (MeO-PBDEs) occur in precipitation, surface water, wildlife, and humans. The formation of OH-PBDEs in wildlife and humans is of considerable concern due to their greater toxicities relative to PBDEs and MeO-PBDEs. Research to date suggests that OH-PBDEs are formed by hydroxylation of PBDEs, and MeO-PBDEs are then formed by methylation of the OH-PBDEs. Here we show significant metabolic production of OH-PBDEs from MeO-PBDEs while hydroxylation of synthetic PBDEs to OH-PBDEs was negligible. Concentrations of PBDEs, OH-PBDEs, and MeO-PBDEs were analyzed in tuna, albatross, and polar bears collected from marine environments worldwide, and we found a closer relationship between OH-PBDEs and MeO-PBDEs than had been previously reported. Furthermore, for the first time the metabolic relationships between PBDEs, OH-PBDEs, and MeO-PBDEs were elucidated in vitro using rainbow trout, chicken, and rat microsomes. We propose the production of OH-PBDEs from naturally occurring MeO-PBDEs as a previously unidentified mechanism that could be an important contributor for the occurrence of OH-PBDEs found in wildlife from remote areas. Our results suggest that risk assessment paradigms for PBDEs and their metabolites need reevaluation and that human exposure to MeO-PBDEs that occur naturally in marine organisms should be considered.

Chemosphere. 2009 Dec; 77(11): 1614-9
Liang B, Lu P, Li H, Li R, Li S, Huang X

The fomesafen degrading bacterium ZB-1 was isolated from contaminated agricultural soil, and identified as Lysinibacillus sp. based on the comparative analysis of 16S rRNA gene. The strain could utilize fomesafen as the sole carbon source for growth, and the total degradation rate was 81.32% after 7 d of inoculation in mineral salts medium. Strain ZB-1 could also degrade other diphenyl ethers including lactofen and fluoroglycofen. The optimum temperature for fomesafen degradation by strain ZB-1 was 30 degrees C. The effect of fomesafen concentration on degradation was also examined. Cell-free extract of strain ZB-1 was able to degrade fomesafen and other diphenyl ethers. Metabolism of fomesafen was accompanied by a transient accumulation of a metabolite identified as [N-[4-{4-(trifluoromethyl)phenoxy}-2-methanamidephenyl]acetamide] using liquid chromatography-mass spectrometry, thus indicating a metabolic pathway involving reduction, acetylation of nitro groups and dechlorination. The inoculation of strain ZB-1 to soil treated with fomesafen resulted in a higher degradation rate than in noninoculated soil regardless of the soil sterilized or nonsterilized.

Curr Eye Res. 2009 Sep; 34(9): 800-8
Jiang D, Gu H, Wu Q, Wang X, Zhang M, Song B

PURPOSE: To investigate whether various sFlt-1 gene fragments affect the biological functions and ERK1/2 pathway of vascular endothelial growth factor (VEGF) under conditions of hypoxia or in the presence of high glucose concentrations in vitro. METHODS: Plasmids expressing loops 2-3 and loops 2-4 of sFlt-1 were packed in carboxymethylated dextran-coated nanoparticles and transferred into human umbilical vein endothelial cells (HUVECs), which were then cultured under hypoxia or in a high-glucose environment. The proliferation and migration of HUVECs were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and low-power microscopy, respectively. Western blot analyses were performed to detect p-ERK1/2 protein expression. RESULTS: After transfection with the sFlt-1(2-3) or sFlt-1(2-4) gene fragment, the proliferation and migration of HUVECs were markedly reduced, and p-ERK1/2 protein expression was down-regulated under both hypoxic and high-glucose conditions. The impacts on the proliferation, migration of HUVECs, and on p-ERK1/2 protein expression did not differ significantly between the sFlt-1(2-3) and sFlt-1(2-4) gene fragments. CONCLUSIONS: Both sFlt-1(2-3) and sFlt-1(2-4) gene fragments inhibited the proliferation and migration of HUVECs, as well as signal transduction in the ERK1/2 pathway of VEGF.

Burns. 2009 Oct 14;
Ge L, Sun L, Chen J, Mao X, Kong Y, Xiong F, Wu J, Wei H

BACKGROUND: It is widely recognised that take of grafts is strongly influenced by tissue viability. Although porcine skin is currently the most widely used xenograft, the viability change of pigskin in vitro has not been extensively studied. The purpose of this study was to assess the change of the viability of Bama miniature pigskin after harvest and cryopreservation, and to set up a guideline for pigskin preservation and storage that would allow the skin to retain the highest viability after treatment and still be used in the clinical applications. METHODS: Harvested pigskin grafts were divided into five groups: normal saline medium/4 degrees C (group 1), Dulbecco's minimum essential medium (DMEM)/4 degrees C (group 2), normal saline medium/25 degrees C (group 3), DMEM/25 degrees C (group 4) and cryopreserved (group 5). In our experiment, the viability was investigated by 3-(4,5)-dimethylthiazol-2,5-diphenyl tetrasolium bromide (MTT) salt assay. We also evaluated the transplantation performance of preserved skin in different conditions by using a rat recipient model, in which primary take was evaluated by gross observation and predetermined histological criteria after 7 days. RESULTS: Skin stored at 4 degrees C showed a very slow viability decrease with time. The sample showed a viability decrease of about 70% after 3 days in normal saline and 4 days in DMEM medium. Nevertheless, skin stored in DMEM at 25 degrees C underwent a viability increase during the first 4h and then decreased gradually to about 70% after 20h, while the viability declined very quickly for skin grafts stored in normal saline medium at 25 degrees C, and maintained the same viability only within 6h of preservation. On the other hand, cryopreserved skin has been shown to maintain a level of skin metabolism equal to 77% of the fresh sample when measured immediately after thawing, and the viability remained about 70% after 6h at 25 degrees C and 2 days at 4 degrees C in DMEM. The graft performance of skin specimens with 70% viability of fresh skin stored in different conditions has not shown statistical significance compared with fresh pigskin. CONCLUSIONS: Based on these results, we suggest that the conservation period of fresh pigskin should not exceed 72 or 96h when stored in normal saline or DMEM at 4 degrees C, and should not exceed 6 or 18h when stored in normal saline or DMEM at 25 degrees C. Cryopreserved pigskin should be stored in DMEM for a maximum period of 48h at 4 degrees C and 6h at 25 degrees C after thawing.

Chem Res Toxicol. 2009 Nov; 22(11): 1802-9
Lupton SJ, McGarrigle BP, Olson JR, Wood TD, Aga DS

While the metabolism and excretion of polybrominated diphenyl ethers (PBDEs) have been reported in rodents, PBDE metabolism in humans has only recently been investigated. In this present study, individual human liver microsomes were incubated for 120 min with radiolabeled and nonradiolabeled BDE 47, 99, or 153 to determine their relative degrees of metabolism and to identify the structures of metabolites formed. Radiolabeled samples were analyzed using high-performance liquid chromatography/radiochemical detection, while nonradiolabeled samples were analyzed with and without derivatization using gas chromatography/mass spectrometry. Results from radiolabeled incubations demonstrated that human liver microsomes metabolized BDEs 47 and 99 but not BDE 153. Differences in the extent of BDE metabolism by the three individual liver specimens used in the study were observed. BDE 47 metabolized to a dihydroxylated BDE 47 and 2,4-dibromophenol, while BDE 99 metabolized to a dihydroxylated BDE 99, 2,4,5-tribromophenol and 1,3-dibromobenzene. This study showed that BDEs 47 and 99 are metabolized by human liver microsomes with relatively large interindividual differences. Results of this study could provide one explanation for the high bioaccumulation rate of BDE 153 in humans.

Chemosphere. 2009 Nov; 77(10): 1358-65
Janzen N, Banzhaf S, Scheytt T, Bester K

A technical scale activated soil filter has been used to study the elimination rates of diverse environmentally relevant micro pollutants from storm and waste water. The filter was made of layers of peat, sand and gravel. The upper (organic) layer was planted with reed (phragmites australis) to prevent clogging and was spiked with activated sludge to enhance microbial biomass and biodegradation potential. Compounds used as UV filters, antioxidants or plasticizers, namely 4-methylbenzylidene camphor (4-MBC), benzophenone-3 (BP-3), butylated hydroxytoluene (BHT), N-butylbenzenesulfonamide (NBBS), 2,6-di-tert-butyl-1,4-benzoquinone (2,6-DTB-1,4-BQ), 1,1-Biphenyl-3,3-dimethyl (1,1-BP-3,3-DM) and dibenzyl (DB) have been included in this study. The chemical characteristics of these compounds ranged from the hydrophilic (pK(OW) 2.6) to the lipophilic (pK(OW) 5) properties. For the elimination studies, synthetic waste water spiked to 3000 ng L(-1) with the selected compounds was used. Elimination rates with low hydraulic load (61 L m(-2)d(-1), water retention time: 2d) were higher than 96%. During a storm water simulation experiment (hydraulic load: 255 L m(-2), water retention time: <1h), the elimination rates of the most analytes decreased to 79-96%. The elimination performance of the hydrophilic compound NBBS declined to 21%. Balancing studies including the soil of the filter system revealed that degradation or transformation were both relevant elimination mechanism.

FEMS Microbiol Lett. 2009 Nov; 301(1): 95-102
Akhtar N, Ghauri MA, Anwar MA, Akhtar K

Out of 17 samples collected from diverse environments, 110 bacterial isolates of varied characteristics were screened for their dibenzothiophene-desulphurizing activity. A single isolate, Eu-32, originating from a soil sample taken from the roots of a eucalyptus tree, displayed dibenzothiophene-desulphurizing activity. This isolate metabolized dibenzothiophene to 2-hydroxyBiphenyl (2-HBP), as detected by HPLC, and was also able to use other organic sulphur compounds as a sole sulphur source. Based on morphological, biochemical and molecular studies, it was found that the organism belongs to the genus Rhodococcus, with a maximum of 95% identity to species in this genus for the partial sequence of the 16S rRNA gene. Isolate Eu-32 could desulphurize 0.2 mM dibenzothiophene to 2-HBP in 72 h at a temperature of 30 degrees C and pH 7.0. The structure and molecular mass of metabolites produced from dibenzothiophene desulphurization were identified by GC-MS, and two sulphur-free products, 2-HBP and Biphenyl, were detected in ethyl acetate extract. It was concluded that isolate Eu-32 is a unique desulphurizing biocatalyst that desulphurizes dibenzothiophene through an extended, sulphur-specific degradation pathway with the selective cleavage of C-S bonds.

Environ Sci Pollut Res Int. 2009 Nov; 16(7): 817-29
Mackova M, Prouzova P, Stursa P, Ryslava E, Uhlik O, Beranova K, Rezek J, Kurzawova V, Demnerova K, Macek T

PURPOSE: Polychlorinated Biphenyls (PCBs) represent a large group of recalcitrant environmental pollutants, differing in the number of chlorine atoms bound to Biphenyl ring. Due to their excellent technological properties, PCBs were used as heat-transfer media, for filling transformers and condensers, as paint additives, etc. With increasing knowledge of their toxicity, transfer to food chains and accumulation in living organisms, their production ended in most countries in the 1970s and in 1984 in the former Czechoslovakia. But even a quarter of century after the PCB production ceased, from contaminated areas, the volatile PCBs evaporate and contaminate much larger areas even at very distant parts of the world. For this reason, PCBs still represent a global problem. The main method of PCB removal from contaminated environment is at present the expensive incineration at high temperatures. With the aim of finding effective alternative approaches, we are studying biological methods for PCB removal from the environment. In this paper, we summarise 10 years of studies using long-term PCB-contaminated soil from a dumpsite in South Bohemia, targeted for the use of plants (phytoremediation) and their cooperation with microorganisms in the root zone (rhizoremediation). MATERIALS AND METHODS: Long-term contaminated soil from Lhenice dumpsite, more than hundred kilograms of homogenised material, was used in microcosms (pots and buckets), and field plots were established at the site. Tested plants include among others tobacco, black nightshade, horseradish, alfalfa and willow. Aseptic plant cell and tissue cultures were from the collection of the IOCB. Microorganisms were our own isolates. The paper summarises experiments done between 1998 and 2008 with real contaminated soil, both vegetated and non-vegetated. PCB analysis was performed by GC-ECD, metabolic products identified mostly using 2D-GC/MS-MS and synthetic standards, whereas molecular methods included quantitative PCR and sequencing. RESULTS: The soil was used both for preparation of field plots at the site and for greenhouse and laboratory tests in microcosms. The results include analyses of changes in PCB content in untreated and vegetated soil, PCB uptake and distribution in different parts of various plant species, analysis of products formed, identification and characterisation of cultivable and non-cultivable bacteria both in rhizosphere and in bulk soil. Different treatments and amendments were also tested. Experiments in real contaminated soil were accompanied by in vitro experiments using aseptic cultures of plant biomass, genetically modified (GM) plants and bacteria, to allow identification of players responsible for PCB metabolisation in soil. The time-span of the experiments allows extrapolating some of the results and drawing conclusions concerning the effectivity of exploitation of various plant species and treatments to remove PCBs from soils. DISCUSSION: The approach using plants proved to represent a viable alternative to costly incineration of PCB-contaminated soils. The recent studies using molecular methods show that plants are responsible for the composition of consortia of microorganisms present in their root zone, including those with ability to degrade the chlorinated aromatic compounds. CONCLUSIONS: In addition to uptake, accumulation and partial metabolisation of PCBs by plants, compounds produced by plants allow survival of microorganisms even in poor soils, serve as carbon and energy source, and can even induce the degradation pathways of different xenobiotics. Thus, the choice of proper plant species is crucial for effective cleaning of different polluted sites. Our study shows how the efficiency of PCB removal is dependent on the plant used. RECOMMENDATIONS AND PERSPECTIVES: The use of plants in biological remediation of different organic xenobiotics proved to be a useful approach. Further improvement can be expected by application of specifically tailored GM plants and use of selective conditions ensuring high remediation potential based on optimal composition of the soil microbial consortia designed for the needs of given site.

Pak J Biol Sci. 2009 Jul 1; 12(13): 957-63
Ebrahimzadeh MA, Nabavi SF, Nabavi SM

Current research into free radicals has confirmed that plants rich in antioxidants play an essential role in the prevention of many diseases. The potential antioxidant activities of Pterocarya fraxinifolia bark and leaves investigated employing six in vitro assay systems. IC50 for DPPH radical-scavenging activities were 3.89 +/- 0.09 for leaves and 41.57 +/- 1.30 microg mL(-1) for bark, respectively. The leaf extract exhibited a good reducing power at 2.5 and 80 microg mL(-1) that was comparable with Vit C (p > 0.05). The extracts also showed weak nitric oxide-scavenging activity and Fe2+ chelating ability. The peroxidation inhibition of extracts exhibited values from 92 to 93% at 72nd h, almost at the same pattern of Vitamin C activity (p > 0.05). Based on higher total phenol and flavonoid contents in leaves, higher antioxidant activities were observed in leaf extract. In addition, chemical composition of leaf essential oil was determined. The major compound was bisabolol oxide A (23.6%). Sesquiterpenes and monoterpenes are the major compounds in leaves essential oil. Presence of these compounds may be a reason for the good antioxidant activity of leaf extract.

Br J Cancer. 2009 Nov 3; 101(9): 1585-95
O'Sullivan-Coyne G, O'Sullivan GC, O'Donovan TR, Piwocka K, McKenna SL

BACKGROUND: Oesophageal cancer incidence is increasing and survival rates remain extremely poor. Natural agents with potential for chemoprevention include the phytochemical curcumin (diferuloylmethane). We have examined the effects of curcumin on a panel of oesophageal cancer cell lines. METHODS: MTT (3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assays and propidium iodide staining were used to assess viability and DNA content, respectively. Mitotic catastrophe (MC), apoptosis and autophagy were defined by both morphological criteria and markers such as MPM-2, caspase 3 cleavage and monodansylcadaverine (MDC) staining. Cyclin B and poly-ubiquitinated proteins were assessed by western blotting. RESULTS: Curcumin treatment reduces viability of all cell lines within 24 h of treatment in a 5-50 muM range. Cytotoxicity is associated with accumulation in G2/M cell-cycle phases and distinct chromatin morphology, consistent with MC. Caspase-3 activation was detected in two out of four cell lines, but was a minor event. The addition of a caspase inhibitor zVAD had a marginal or no effect on cell viability, indicating predominance of a non-apoptotic form of cell death. In two cell lines, features of both MC and autophagy were apparent. Curcumin-responsive cells were found to accumulate poly-ubiquitinated proteins and cyclin B, consistent with a disturbance of the ubiquitin-proteasome system. This effect on a key cell-cycle checkpoint regulator may be responsible for the mitotic disturbances and consequent cytotoxicity of this drug. CONCLUSION: Curcumin can induce cell death by a mechanism that is not reliant on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of oesophageal cancer.

Circ Heart Fail. 2009 Sep; 2(5): 446-55
Kassiri Z, Zhong J, Guo D, Basu R, Wang X, Liu PP, Scholey JW, Penninger JM, Oudit GY

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that metabolizes Ang II into Ang 1-7, thereby functioning as a negative regulator of the renin-angiotensin system. We hypothesized that ACE2 deficiency may compromise the cardiac response to myocardial infarction (MI). METHODS AND RESULTS: In response to MI (induced by left anterior descending artery ligation), there was a persistent increase in ACE2 protein in the infarct zone in wild-type mice, whereas loss of ACE2 enhanced the susceptibility to MI, with increased mortality, infarct expansion, and adverse ventricular remodeling characterized by ventricular dilation and systolic dysfunction. In ACE2-deficient hearts, elevated myocardial levels of Ang II and decreased levels of Ang 1-7 in the infarct-related zone was associated with increased production of reactive oxygen species. ACE2 deficiency leads to increased matrix metalloproteinase (MMP) 2 and MMP9 levels with MMP2 activation in the infarct and peri-infarct regions, as well as increased gelatinase activity leading to a disrupted extracellular matrix structure after MI. Loss of ACE2 also leads to increased neutrophilic infiltration in the infarct and peri-infarct regions, resulting in upregulation of inflammatory cytokines, interferon-gamma, interleukin-6, and the chemokine, monocyte chemoattractant protein-1, as well as increased phosphorylation of ERK1/2 and JNK1/2 signaling pathways. Treatment of Ace2(-)(/y)-MI mice with irbesartan, an AT1 receptor blocker, reduced nicotinamide-adenine dinucleotide phosphate oxidase activity, infarct size, MMP activation, and myocardial inflammation, ultimately resulting in improved post-MI ventricular function. CONCLUSIONS: We conclude that loss of ACE2 facilitates adverse post-MI ventricular remodeling by potentiation of Ang II effects by means of the AT1 receptors, and supplementing ACE2 can be a potential therapy for ischemic heart disease.

Environ Sci Technol. 2009 Sep 15; 43(18): 6963-8
Zhu L, Ma B, Hites RA

In 2006, 128 serum samples were collected from three populations in Tianjin, China: office cleaners, university students, and policemen. These samples were all analyzed for polybrominated diphenyl ethers (PBDEs) and for other brominated flame retardants (BFRs). The median concentration of total PBDEs (sum of 41 congeners) was 7.1 ng/g lipid, ranging from 0.48 to 1980 ng/g lipid. Among these PBDE congeners, the median sum of the tri- to hepta-PBDE (SigmaPBDE3-7) congener concentrations was 2.9 ng/g lipid, ranging from 0.48 to 20 ng/g lipid. The most common tri- to heptabrominated congeners were BDE-47 (30% of total), BDE-99 (24%), BDE-183 (15%), BDE-153 (12%), BDE-28 (9.5%), and BDE-100 (6.2%). These levels of SigmaPBDE3-7 were similar to those observed in Europe and Asia but were much lower than those observed in North America. Highly brominated BDE congeners were detected in some serum samples. In particular, BDE-209 was detected in 28 samples; the median BDE-209 concentration in these samples was 42 ng/g lipid, ranging from ND to 1770 ng/g lipid. The total PBDE levels in office cleaners were significantly higher than in university students and policemen. In addition, we also measured several other BFRs. Hexabromobenzene (HBB) was identified in 26 samples with a median concentration of 0.27 ng/g lipid, ranging from 0.11 to 1.50 ng/g lipid. Pentabromoethylbenzene (PBEB), hexabromocyclododecane (HBCD), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), and decabromodiphenylethane (DBDPE) were not detected in any of these samples.

Environ Sci Technol. 2009 Sep 15; 43(18): 6956-62
Gao F, Luo XJ, Yang ZF, Wang XM, Mai BX

Concentrations of several persistent organohalogen compounds such as dichlorodiphenyltrichloroethane and its metabolites (DDTs), hexachlorocyclohexanes (HCHs), polychlorinated Biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), decabromodiphenylethane (DBDPE), and polybrominated Biphenyl 153 (PBB 153) were measured in eggs of six species of wild aquatic birds, one species of wild terrestrial bird, and two species of captive birds from North China. Among the contaminants measured, DDTs were the dominant compounds, HCHs and PCBs were in nearly the same concentration range, and PBDEs exhibited lower concentrations than other compound groups. The median concentrations of DDTs, HCHs, PCBs, and PBDEs in all avian species ranged from 21 to 11034, 5.5 to 623, 1.0 to 613, and 4.6 to 146 ng/g lipid wt, respectively. Median concentrations of DBDPE and PBB 153 in all avian species were in the range of not detectable (ND)-1.7 and ND-0.7 ng/g lipid wt, respectively. Significant differences among species in contaminant profiles and contaminant levels were found depending on their feeding habits, habitat, and migration. The captive birds had the lowest contaminant levels and entirely different congener profiles in PCBs and PBDEs from those of wild birds, which can be attributed to differences in dietary compositions and reproduction rates. Octa- to deca-BDEs contributed more to the total PBDEs in wild terrestrial and captive birds than in wild aquatic birds, except for one insectivorous species, possibly due to greater exposure to terrestrial food sources. Preliminary risk assessment suggests that there is no risk of a reduction in offspring survival in avian species from North China due to organohalogen compounds, except for dichlorodiphenyldichloroethylene (DDE), which would be expected to affect some proportion of the populations of several species of birds studied.

Environ Sci Technol. 2009 Sep 15; 43(18): 6944-9
Lam JC, Lau RK, Murphy MB, Lam PK

Concentrations of hexabromocyclododecanes (HBCDs), polybrominated diphenyl ethers (PBDEs), and three novel flame retardants, namely2-ethylhexyl 2,3,4,5-tetrabromobenzoate (TBB), bis-(2-ethylhexyl)-tetrabromophthalate (TBPH), and hexachlorocyclopentadienyldibromocyclooctane (HCDBCO), were determined in blubber samples of Indo-Pacific humpback dolphins (Sousa chinensis) and finless porpoises (Neophocaena phocaenoides). The levels of HBCDs and PBDEs in cetacean samples ranged from 4.1 to 519 and 103 to 51,100 ng/g lw, respectively. A significant increasing trend of SigmaHBCDs was observed in dolphin samples from 1997 to 2007 with an estimated annual rate of 5%, whereas no significant temporal trends of SigmaPBDEs appeared over the sampling period. This pattern may be attributed to the increasing usage of HBCDs following the restriction/voluntary withdrawal of the production and use of PBDE commercial mixtures in several countries. HCDBCO was not found in the blubber samples. This is the first report of the presence of TBB and TBPH, two new flame retardants that have previously been identified in house dust from the U.S., in marine mammals; concentrations of these compounds in dolphins and porpoises ranged from the instrumental detection limit (IDL) (<0.04) to 70 and IDL (<0.04) to 3859 ng/g lw, respectively. Levels of TBPH were comparable to SigmaHBCDs in porpoise samples. The presence of these novel flame retardants in top-trophic-level marine organisms raises concern about their release into the environment and indicates the need for further monitoring of these compounds in other environmental matrices.

Chemosphere. 2009 Nov; 77(9): 1199-205
Sun K, Zhao Y, Gao B, Liu X, Zhang Z, Xing B

Limited information on the levels, inventory and fate of Organochlorine pesticides (OCPs) and Polybrominated diphenyl ethers (PBDEs) in the soils irrigated by sewage or wastewater is available. In this study, variation in concentrations, profiles and fate of OCPs and PBDEs were investigated using soil samples collected from a region irrigated by sewage, mixed water and clean water in the east of Beijing, China. No significant variation was observed among groups, except for penta-BDEs. The measured SigmaOCPs and SigmaPBDEs residues ranged from 6.4 to 171.2 ng g(-1) (dw) and 501.9 to 3310.7 pg g(-1) (dw), respectively. SigmaDDTs and BDE-209 were the most abundant congeners accounting for about 76% of SigmaOCPs and 93% of SigmaPBDEs. Concentrations of hexachlorocyclohexanes (HCHs), dichlorodiphenyltrichloroethane (DDTs) and its major degradation products, and hexachlorobenzene (HCB) ranged from 1.2 to 11.4 ng g(-1) (dw), 4.0 to 155.6 ng g(-1) (dw) and 0.3 to 3.4 ng g(-1) (dw), respectively. The major DDT degradation products were p,p'-DDT and p,p'-DDE. The major hexachlorocyclohexane (HCH) isomer in irrigated soils is beta-HCH, reflecting its higher affinity to solids and resistance to degradation than other isomers. Both alpha-HCH/beta-HCH and p,p'-DDT/p,p'-DDE ratios were log-normally distributed and negatively correlated to log(SigmaHCHs) and log(SigmaDDTs), respectively, suggesting no significant recent application of OCPs. Individual BDE congeners, SigmaPBDEs and SigmaOCPs were significantly correlated with total organic carbon (TOC). Moreover, a good correlationship between SigmaPBDEs and black carbon (BC) was obtained but not between SigmaOCPs and BC. Sewage irrigation did not have obvious effect on their contaminant levels and inventory of OCPs and PBDEs.