p,p'-DDE与雄激素受体突变体H874Y及T877A激动性作用机制的理论研究

1,1-二氯-2,2-双(对氯苯基)乙烯(p,p'-DDE)是一种已知的雄激素受体(androgen receptor,AR)拮抗剂。有趣的是,已有研究证实p,p'-DDE同时可经由作用于AR的2种天然突变体H874Y和T877A产生拟雄激素效应,但其相互作用的分子机制尚不清晰。本研究联用分子动力学模拟与MM-GBSA方法,以内源性激素二氢睾酮(DHT)作为对照,对p,p'-DDE与2种突变体的相互作用分子机制进行了研究。模拟结果指出范德华相互作用是维持p,p'-DDE与AR突变体结合的主要驱动力,而溶剂化作用的差异是导致p,p'-DDE与H874Y具有较高结合活性的主要原因,H874Y结合口袋与p,p'-DDE的结构匹配度优于与T877A。与内源性配体二氢睾酮相比较,范德华作用与静电相互作用的差异是造成p,p'-DDE比DHT结合活性低的主要原因,p,p'-DDE与AR突变体之间缺乏氢键的稳定。MM-GBSA的结果确定p,p'-DDE与突变体结合过程的关键氨基酸以疏水性残基为主,其中L704、M745、L873尤为重要。计算获得的p,p'-DDE对H874Y及T877A相互作用分子机制有助于理解该污染物在不同人群中内分泌干扰效应的差异。     

Contribution of sociodemographic characteristics, occupation, diet and lifestyle to DDT and DDE concentrations in serum and adipose tissue from a Bolivian cohort

The organochlorine pesticide p,p′-Dichlorodiphenyltrichloroethane (DDT) was widely used in the early 1960s-70s for vector control in tropical and subtropical areas of South America. Due to its persistence, DDT has a high potential to bioaccumulate in the food chain and living organisms and is a major public health concern, especially in South America.The main purpose of the present study was to investigate predictors of serum and adipose tissue concentrations of p,p′-DDT and its main metabolite, p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE), in an adult cohort (n = 112) from Santa Cruz de la Sierra, Bolivia, using multiple linear regression models. These models explained 29.3-47.8% of the variability in adipose tissue concentrations of p,p′-DDT and p,p′-DDE, respectively, and 32.9-47.0% of that in serum. Main exposure predictors included age, occupational class, residence, diet, smoking habit, and accumulated breastfeeding time.This is one of the few studies to explore predictors of human exposure to these chemicals using a multivariate approach in a South American population. Results show that predictors of human exposure to p,p′-DDT and p,p′-DDE in Santa Cruz de la Sierra may diverge from those found in other populations of the world, due to particular sociodemographic and lifestyle characteristics of this region.     

Levels of Persistent Organochlorine Residues in Eggs of Greater Flamingos from the Guadalquivir Marshes (Doñana), Spain

Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) residue levels were determined in 53 unhatched eggs from greater roseus flamingos (Phoenicopterus ruber). Eggs were collected in 1996 from the National Park of Doñana (Guadalquivir marshes, Southwest Spain), immediately after one breeding colony abandoned the nesting site due to predator attacks. The main metabolite of p,p′-DDT, p,p′-DDE, was the OCP residue found at higher concentrations, with a geometric mean of 721 ng/g wet weight. Residues of other pesticides, including some hexachlorocyclohexane isomers, hexachlorobenzene, aldrin, heptachlor, and heptachlor-epoxide, were detected at much lower concentrations. The sum of PCBs was 528 ng/g, with PCB congeners #187 and #153 being the most prominent in eggs. The pattern observed in these compounds of industrial origin corresponded more to Aroclor 1260 than to any other commercial mixture. Levels of organochlorine residues indicate a medium degree of exposure, and they are not considered of any concern for the flamingo population. In particular, neither p,p′-DDE nor PCB levels were found to be correlated with the eggshell thickness.     

Levels of persistent organic pollutant and their predictors among young adults

Exposure to persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethane (p,p′-DDE), and hexachlorobenzene (HCB) continues to be of concern due to their ubiquitous distribution and high persistence. Current toxicant body burden is still a primary concern within the Akwesasne Mohawk Nation since other studies conducted within the community have shown relationships between these POPs and endocrine disruption.In this article we describe the levels of these toxicants in young adults of the Akwesasne Mohawk Nation between the ages of 17 and 21 years of age (mean age 18.1 years), and investigate potential influences of their current body burden. Seventeen congeners in fourteen chromatographic peaks were detected in 50% or more of the individuals sampled (geometric mean [GM] of the sum of these congeners = 0.43 ppb). Congeners 118, 138[+163 + 164] and 153 had the highest rate of detection (?98%) within the Akwesasne young adults. Of the other organochlorines, HCB (GM = 0.04 ppb) and p,p′-DDE (GM = 0.38 ppb) were found in 100% and 99% of the sample respectively.Significantly higher levels of PCBs were found among individuals who were breastfed as infants, were first born, or had consumed local fish within the past year. When compared to levels of p,p′-DDE, HCB, and 13 specific congeners reported by the CDC for youth between the ages of 12 and 19 years, the geometric means of several congeners (CBs 99, 105, 110, and 118) among the Akwesasne were higher than the reported CDC 90th percentile. In contrast, levels of CB 28 in Akwesasne young adults were ∼50% or less than those of the CDC cohort. p,p′-DDE and HCB levels were generally higher in the CDC cohort (GM of 0.516 and 0.065 ppb, respectively for Mohawks vs. 2.51 and 0.123, respectively, for CDC). Concentrations of non-persistent PCBs among this sample of Akwesasne young adults were higher than those reported by the CDC suggesting continued exposure, but lower than those associated with severe contamination.Additional research into the concentration trends of individual PCB congeners within Akwesasne youth and young adults is warranted to further improve our insight into the determinants and influences of organochlorine concentrations within members of the Akwesasne community.     

Influence of plant-earthworm interactions on SOM chemistry and p,p'-DDE bioaccumulation

Laboratory experiments assessed how bioaccumulation of weathered p,p′-DDE from soil and humic acid (HA) chemistry are affected by interactions between the plants Cucurbita pepo ssp. pepo and ssp. ovifera and the earthworms Eisenia fetida, Lumbricus terrestris, and Apporectodea caliginosa. Total organochlorine phytoextraction by ssp. pepo increased at least 25% in the presence of any of the earthworm species (relative to plants grown in isolation). Uptake of the compound by ssp. ovifera was unaffected by earthworms. Plants influenced earthworm bioaccumulation as well. When combined with pepo, p,p′-DDE levels in E. fetida decreased by 50%, whereas, in the presence of ovifera, bioconcentration by L. terrestris increased by more than 2-fold. Spectral analysis indicated a decrease in hydrophobicity of HA in each of the soils in which both pepo and earthworms were present. However, HA chemistry from ovifera treatments was largely unaffected by earthworms. Risk assessments of contaminated soils should account for species interactions, and SOM chemistry may be a useful indictor of pollutant bioaccumulation.     

Persistent Organochlorine Residues in Livers of Six Species of Ciconiiformes (Aves) from Spain

Liver samples of 42 birds belonging to 6 species of Ciconiiformes (grey heron (n = 17), little egret (n = 12), cattle egret (n = 1), glossy ibis (n = 1), little bittern (n = 1), and white stork (n = 10)), collected from two different zones of Spain (Ebro Delta and Madrid) in 1992–1997, were analyzed for organochlorine pesticides and PCBs. ΣPCBs (sum of concentrations of individual congeners), p,p′-DDE, HCB, γ-HCH, and heptachlor epoxide were the most prevalent residues detected in all samples (occurrence > 95%). There were no statistically significant differences in organochlorine levels between grey herons and little egrets, while levels of ΣPCBs, p,p′-DDE, HCB, γ-HCH, and heptachlor were significantly lower for white storks. These results could be explained by the different habitat of these species, aquatic in the Ebro Delta (grey herons, little egrets) and dry in Madrid (white stork), and their diverse feeding habits.     

Polybrominated diphenyl ethers,polychlorinated dibenzo-dioxins,-furans,and-biphenyls in three species of antarctic penguins

Background, Aims and Scope Fish-eating seabirds are recognized to be at risk of accumulating toxic contaminants due to their high position in the trophic web and to their low ability to metabolize xenobiotic compounds. Penguins are widely distributed in Antarctica and represent an important fraction of the Antarctic biomass. They feed mainly on krill and, depending on krill availability, also on fish. It has been reported that predators may be a sink for volatile and toxic chemicals and this may pose a serious environmental problem. Polybrominated diphenyl ethers (PBDEs), polychlorinated dibenzo-dioxins (PCDDs),-furans (PCDFs), and-biphenyls (PCBs), including non-ortho congeners, hexachlorobenzene (HCB) and p,p′-DDE, were quantified in three species of Antarctic Pygoscelids in order to evaluate their accumulation patterns. The potential toxicity of twenty-two dioxin-like congeners was assessed and expressed as 2,3,7,8-tetraCDD equivalents (TEQs). Differences between males and females were investigated. Methods Blood samples of the Adélie penguin Pygoscelis adeliae, Chinstrap penguin Pygoscelis antarctica and Gentoo penguin Pygoscelis papua were collected at Admiralty Bay, King George Is (62°10′39″ S, 58°26′46″ W) in February 2004. Halogenated hydrocarbons were identified and quantified using gas chromatography coupled with gas chromatography mass spectrometry analyses. Results are expressed on a wet weight basis. Results and Discussion HCB, p,p′-DDE and ΣPCBs were higher in Adélie penguins (6.7±6.1, 8.2±3.3 and 9.8±3.8 ng/g, respectively) than in Chinstrap and Gentoo penguins, both of which showed values in the same order of magnitude, but approximately 40% lower than Adélie penguins. Hexa-CBs ranged 35–45% of the residue. Low-chlorinated PCBs (nos. 70+76+95+56+60+101) accounted for 40–60% in the three species. PCB101 made up 15% of the residue in Adélie penguins. PBDEs were 291±477, 107±104 and 116±108 pg/g in Adélie, Chinstrap and Gentoo penguins, respectively; the most abundant congeners were BDE47 in Adélie and Chinstrap penguins and BDE17 in Gentoo penguins. PCDDs were 22±32, 6.5±7.4 and 18±23 pg/g in Adélie, Chinstrap and Gentoo penguins, respectively. PCDFs were higher in Adélie penguins and lower in Chinstrap penguins. PCDDs/Fs and PBDEs were higher in males than in females of Gentoo and Chinstrap penguins; differences in concentrations were likely related to the partial detoxification that occurs in females during egg formation. Of the four non-ortho PCBs measured, PCB126 occurred at the highest concentrations and contributed the majority of the non-ortho PCB-TEQ in Gentoo and Chinstrap penguins. The highest TEQs were found in the Gentoo penguin and due mainly to PCDDs and non-ortho PCBs. Conclusions POP concentrations in penguins were lower than those found in seabird species from other areas of the world. Different chemical accumulation patterns were observed in relation to species and sex; the Adélie penguin showed the highest POP levels. Dissimilar ecological or metabolic features may be involved; the diverse timing of reproduction steps can be responsible for those differences; moreover, Adélie penguins feed on krill (a fatty resource) more abundantly than the other two species during the rearing period. Recommendation and Outlook The South Shetland Islands might be subjected to a higher chemical impact with respect to the rest of Antarctica, due to their being near South America. Because penguins are fish-eating birds showing low detoxifying capacities and key-species in Antarctic ecosystems, further studies on their xenobiotic metabolism should be carried out.     

Metabolism of DDT in Different Tissues of Young Rats

The bioconcentration and distribution pattern of p,p′-DDT 1,1,1-1trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)-ethane] and its main metabolites (p,p′-DDD [1,1-dichloro-2,2-bis (4-chlorophenyl) ethane] and p,p′-DDE [1,1-dichloro-2,2-bis (4-chlorophenyl) in adipose tissue, liver, brain, kidney, thymus, and testis were examined in young rats after 10 days of intraperitoneal injection of 50 and 100 mg of p,p′-DDT/kg of body weight. Analyses were performed by high-resolution gas chromatography. p,p′-DDT was found to be accumulated in a dose-dependent manner with the highest concentration in adipose tissue. However, in brain, the accumulation of pesticide was low and remained unchanged at the higher dose. This difference may relate to the protective role of the blood-brain barrier, which limits the access of the xenobiotic in the cerebral compartment, and to the differential tissue lipid composition. Although tissues concentration of p,p′-DDE and p,p′-DDD correlated positively to total p,p′-DDT levels, the active role in detoxification of pollutants may explain why p,p′-DDD is more abundant in liver than in the rest of organs. On the contrary, in brain, the concentration of p,p′-DDE is higher than that of p,p′-DDD, suggesting that the metabolism of the parent insecticide proceeds via more than one pathway.     

Anaerobic transformation of four abundant organochlorine pesticide residues (B8-1413, B9-1679, oxychlordane,p,p‵-DDE) in extracts of Antarctic skua eggs by the isolated bacterium Sulfurospirillum multivorans

Residues of halogenated pollutants bioaccumulated in eggs of the south polar skua (Catharacta maccormicki) from the Antarctic were extracted, purified, and fractionated. The target fraction which contained the bulk of the chloropesticides was concentrated and incubated with cell suspensions of the isolated bacterium Sulfurospirillum multivorans (formerly Dehalospirillum multivorans). S. multivorans was previously identified as a good anoxic transformer of several halogenated compounds. The compounds of technical toxaphene 2-endo,3-exo,5-endo,6-exo,8,8,10,10-octachlorobornane (B8-1413, also known as P-26) and 2-endo,3-exo,5-endo,6-exo,8,8,9,10,10-nonachlorobornane (B9-1679, also known as P-50) as well as 1,1-dichloro-2,2-bis(p-chlorophenyl)ethene (p,p′-DDE) and 1-exo,2-exo,4,5,6,7,8,8-octachloro-2,3-exo-epoxy-3a,4,7,7a-tetrahydro-4,7-methanoindene (oxychlordane) were present at a sufficiently high concentration and hence useful for studying the anaerobic transformation by the bacterium. When treated with S. multivorans, B8-1413 and B9-1679 were almost quantitatively transformed within 1 day. For B9-1679, the major metabolite was found to be 2-endo,3-exo,5-endo,6-exo,8,9,10-heptachlorobornane (B7-1001). Compared to the toxaphenes, transformation of oxychlordane and p,p′-DDE was significantly slower. Even after seven days, about 10% of the initial pool was detected in the extracts. 1-chloro-2,2-bis(p-chlorophenyl)ethene (p,p′-DDMU) was identified as a transformation product of p,p′-DDE. The four compounds in this study comprise some of the most persistent chloropesticide residues found in marine birds. In case there is sufficient transformation before they reach the top predators, the bioaccumulative potential can be significantly reduced.     

Sorption of 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane (DDT) by clays and organoclays

This study focused on the sorption isotherms of 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane (p,p'-DDT) and 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE) on different original clays (i.e., zeolite, montmorillonite and attapulgite) and organoclay complexes. Sorption of organic pollutants was determined using gas chromatographic (GC) techniques to investigate the sorption behavior, and characterize the effect of, different organic cations. The original clays only sorbed low amounts of p,p'-DDT and p,p'-DDE, and the sorptive curves can be classified as L-shaped. Organoclays exhibited higher amounts of p,p'-DDT and p,p'-DDE sorption. The p,p'-DDT and p,p'-DDE sorption increased with increasing total organic carbon (OC) content of the organoclays. For hexadecyltrimethylammonium (HDTMA)-modified organoclays, the dominant adsorptive medium showed the partitioning sorption of hydrophobic-hydrophobic interaction, indicating no competitive sorption. The sorptive curves can be classified as C-shaped of constant partition (CP). However, benzyltrimethylammonium (BTMA)-modified organoclays exhibited competitive sorption. The sorption isotherm curves can be classified as S-shaped. The sorptive capacity of the HDTMA-modified organoclays for p,p'-DDT were higher than those for p,p'-DDE, but the BTMA-modified organoclays showed a reverse trend. This can be attributed to the different structures and shapes of organic cations, giving different sorptive mechanisms. The p,p'-DDT and p,p'-DDE sorption onto HDTMA-modified organoclays were caused by chemical interaction, with the BTMA modified organoclays occuring due to physical sorption.