The metabolic activation of pentachlorophenol to chloranil as a potent inhibitor of human and rat placental 3ß-hydroxysteroid dehydrogenases.

Pentachlorophenol (PCP) is a widely used pesticide. However, whether PCP and its metabolite chloranil have endocrine-disrupting effects by inhibiting placental 3ß-hydroxysteroid dehydrogenase 1 (3ß-HSD1) remains unclear. The study used in vitro assays with human and rat placental microsomes to measure 3ß-HSD activity as well as human JAr cells to evaluate progesterone production. The results showed that PCP exhibited moderate inhibition of human 3ß-HSD1, with an IC50 value of 29.83 µM and displayed mixed inhibition in terms of mode of action. Conversely, chloranil proved to be a potent inhibitor, demonstrating an IC50 value of 147 nM, and displaying a mixed mode of action. PCP significantly decreased progesterone production by JAr cells at 50 µM, while chloranil markedly reduced progesterone production at ≥1 µM. Interestingly, PCP and chloranil moderately inhibited rat placental homolog 3ß-HSD4, with IC50 values of 27.94 and 23.42 µM, respectively. Dithiothreitol (DTT) alone significantly increased human 3ß-HSD1 activity. Chloranil not PCP mediated inhibition of human 3ß-HSD1 activity was completely reversed by DTT and that of rat 3ß-HSD4 was partially reversed by DTT. Docking analysis revealed that both PCP and chloranil can bind to the catalytic domain of 3ß-HSDs. The difference in the amino acid residue Cys83 in human 3ß-HSD1 may explain why chloranil is a potent inhibitor through its interaction with the cysteine residue of human 3ß-HSD1. In conclusion, PCP is metabolically activated to chloranil as a potent inhibitor of human 3ß-HSD1.

Co-exposure to pentachlorophenol (PCP) and cadmium (Cd) triggers apoptosis-like cell death in Eschericia coli.

Pentachlorophenol (PCP) - cadmium (Cd) complex pollution has been identified as a form of persistent soil pollution in south China, exerting detrimental impacts on the indigenous soil bacterial communities. Hence, it is worthwhile to investigate whether and how bacterial populations alter in response to these pollutants. In this study, Escherichia coli was used as a model bacterium. Results showed that PCP exposure caused bacterial cell membrane permeability changes, intracellular ROS elevation, and DNA fragmentation, and triggered apoptosis-like cell death at low exposure concentration and necrosis at high exposure concentration. Cd exposure caused severe oxidative damage and cell necrosis in the tested bacterial strain. The co-exposure to PCP and Cd elevated the ROS level, stimulated the bacterial caspase activity, and induced DNA fragmentation, thereby leading to an apoptosis-like cell death. In conclusion, PCP-Cd complex pollution can cause bacterial population to decrease through apoptosis-like cell death pathway. However, it is worth noting that the subpopulation survives under the complex pollution stress.

Nano-TiO2 aggravates the adverse effect of pentachlorophenol on antioxidant and immune response in anti-predatory mussels.

Nano-TiO2 can act as a vector to organic compounds, such as pentachlorophenol (PCP) posing a potential threat to the marine ecosystems. Studies showed that nano pollutant toxicity can be modulated by abiotic factors, but little is known about the potential influence of biotic stressors (such as predators) on the physiological responses to pollutants in marine organisms. We explored the effects of n-TiO2 and PCP on the mussel Mytilus coruscus in the presence of its natural predator, the swimming crab Portunus trituberculatus. Exposure to n-TiO2, PCP, and predation risk showed interactive effects on antioxidant and immune parameters of the mussels. Elevated activities of catalase (CAT), glutathione peroxidase (GPX), acid phosphatase (ACP) and alkaline phosphatase (AKP), suppressed activity of superoxide dismutase (SOD), lower levels of glutathione (GSH) and increased malondialdehyde (MDA) levels indicated dysregulation of the antioxidant system and immune stress induced by single PCP or n-TiO2 exposure. Integrated biomarker (IBR) response values showed the effect of PCP was concentration dependent. Of the two used n-TiO2 sizes (25 and 100 nm), larger particles induced higher antioxidant and immune disturbances indicating higher toxicity possibly due to higher bioavailability. Compared to single PCP exposure, the combination of n-TiO2 and PCP enhanced the imbalance of SOD/CAT and GSH/GPX and led to elevated oxidative lesions and activation of immune-related enzymes. Overall, the combined impacts of pollutants and biotic stress exhibited a greater magnitude of adverse effects on antioxidant defense and immune parameters in mussels. The toxicological effects of PCP were exacerbated in the presence of n-TiO2, and the deleterious impact of these stressors was further amplified under predator-induced risk after prolonged (28 days) exposure. However, the underlying physiological regulatory mechanisms governing the interplay of these stressors and predatory cues on mussels remain elusive, warranting further investigation.

Pentachlorophenol causes redox imbalance, inhibition of brush border membrane and metabolic enzymes, DNA damage and histological alterations in rat kidney.

Pentachlorophenol (PCP) is a synthetic organochlorine compound that is widely used in biocide and pesticide industries, and in preservation of wood, fence posts, cross arms and power line poles. Humans are usually exposed to PCP through air, contaminated water and food. PCP enters the body and adversely affects liver, gastrointestinal tract, kidney and lungs. PCP is a highly toxic class 2B or probable human carcinogen that produces large amount of reactive oxygen species (ROS) within cells. This work aimed to determine PCP-induced oxidative damage in rat kidney. Adult rats were given PCP (25, 50, 100, 150 mg/kg body weight), in corn oil, once a day for 5 days while control rats were given similar amount of corn oil by oral gavage. PCP increased hydrogen peroxide level and oxidation of thiols, proteins and lipids. The antioxidant status of kidney cells was compromised in PCP treated rats while enzymes of brush border membrane (BBM) and carbohydrate metabolism were inhibited. Plasma level of creatinine and urea was also increased. Administration of PCP increased DNA fragmentation, cross-linking of DNA to proteins and DNA strand scission in kidney. Histological studies supported biochemical findings and showed significant damage in the kidneys of PCP-treated rats. These changes could be due to redox imbalance or direct chemical modification by PCP or its metabolites. These results signify that PCP-induced oxidative stress causes nephrotoxicity, dysfunction of BBM enzymes and DNA damage.

Human health ambient water quality criteria and risk assessment of pentachlorophenol in Poyang Lake Basin, China.

Pentachlorophenol (PCP) has been widely used as an insecticide for killing oncomelania (the intermediate host of schistosome) in China and leads to severe environmental contamination. Poyang Lake, as the largest freshwater lake and bird habitat in China, was once a schistosomiasis epidemic area. In this study, the concentrations of PCP in water and aquatic products from Poyang Lake were determined and analyzed, and then the human health ambient water quality criteria (AWQC) was derived based on native parameters of Poyang Lake basin. Finally, a comprehensive analysis of the health risks of drinking water and different types of aquatic products consumption was carried out. The results showed that PCP concentrations were ranged from 0.01 to 0.43 µg/L in surface water and 3.90 to 85.95 µg/kg in aquatic products. Due to the carcinogenicity of PCP, the human health AWQC for PCP are 0.02 µg/L for consumption of water and organisms and 0.03 µg/L for consumption of organisms only. Deterministic and probabilistic risk analysis indicated that the non-carcinogenic risk of PCP were acceptable in Poyang Lake, while the carcinogenic risk cannot be ignored. The health risks of PCP caused by aquatic products consumption were higher than that by drinking water. The percentages of acceptable risk for the population in Poyang Lake Basin were 99.95% at acceptable level of 10-4. Based on the sensitivity analysis, the impact of PCP concentrations on health risk values ranged from 53 to 82%. The study provided valuable information for regional water quality criteria development and water quality assessment.

Variability, determinants, and associations with oxidative stress biomarkers of pentachlorophenol among Chinese pregnant women: A longitudinal study.

Pentachlorophenol (PCP) is ubiquitous and moderately persistent in the environment, and it is an identified human carcinogen. Previous animal experiments indicate that toxic mechanisms of PCP include oxidative stress. However, no epidemiological study has reported the association between PCP exposure and oxidative stress; such association in pregnant women, a vulnerable population, is of particular interest. This study aimed to characterize PCP concentrations in 2304 urine samples from 768 pregnant women, explore its determinants, and evaluate the associations between PCP exposure and three oxidative stress biomarkers across three trimesters. The median concentrations of PCP (100% detected) in the first, second, and third trimester were 0.61, 0.59, and 0.48 ng/mL, respectively, with a significant decrease trend. The intraclass correlation coefficient of specific gravity (SG)-adjusted PCP was 0.26, indicating high variability for PCP across the three trimesters. PCP concentrations were significantly higher in older, pre-pregnancy overweight, multiparous, high-income, and employed women during pregnancy. Urinary PCP was markedly lower in samples collected during spring compared to other seasons. Linear mixed effect models for repeated measures revealed that ln-transformed SG-adjusted PCP was significantly associated with increased 8-hydroxy-2'-deoxyguanosine (8-OHdG; percent change [%Δ] caused by each interquartile range increase of PCP: 46.2, 95% confidence interval [CI]: 40.2, 52.5) and 8-hydroxyguanosine (8-OHG;%Δ [95% CI]: 44.8 [40.1, 49.8]), but the positive association with 4-hydroxy2-nonenal-mercapturic acid (HNE-MA) was not significant. PCP was also positively associated with increased 8-OHdG and 8-OHG in each trimester using general linear models, and its associations with HNE-MA were only significant at T1 (%Δ [95% CI]: 19.1 [1.05, 40.3]) and T2 (%Δ [95% CI]: 12.6 [0.32, 26.3]). Our findings provide valuable information about PCP exposure characteristics during pregnancy and the potential effects of PCP exposure on oxidative stress in pregnant women.

Pentachlorophenol mediated regulation of DAMPs and inflammation: In vitro study.

Pentachlorophenol (PCP) was once a widely employed organochlorine pesticide and wood preservative in United States. Due to its toxicity, the U.S. Environmental Protection Agency has classified it as a restricted-use pesticide and established as a liver carcinogen. Earlier reports have indicated increased production of inflammatory mediators like IL-1ß and TNF-α by immune cells, including NK cells, lymphocytes, or monocytes -on PCP exposure. Yet, there is only scant information available regarding the detailed molecular mechanisms affected by acute or chronic exposure of humans to PCP. Considering this, we examined PCP-induced inflammation and downstream signaling events in-(a) human lung adenocarcinoma cells (A549) with type II alveolar epithelial characteristics; and (b) human liver carcinoma cells (HepG2). Treatment of these cells with 1 µM and 10 µM concentration of PCP for 24 h duration resulted in a significant induction of cytokines/chemokines including IL-1ß, IL-6, TNF-α, IL-8, CCL2, and CCL5. Assessment of mRNA expression showed upregulated levels of danger-associated molecular patterns (DAMPs)-high mobility group box-1 (HMGB1) and heat shock protein 70 (Hsp70) as well as TLR-4 receptor in PCP-challenged cells. Increased expression of transcription factors-NF-κB and STAT3 provide further insight into the molecular mechanisms underlying PCP-induced toxicity/pathology. Interestingly, antibody-mediated neutralization of DAMPs abrogates PCP-mediated transcriptional induction of cytokines, chemokines and transcription factors in HepG2 and A549 cells. Overall, our findings demonstrate the important role of DAMPs in PCP-induced inflammatory responses.

Pentachlorophenol has significant adverse effects on hematopoietic and immune system development in zebrafish (Danio rerio).

In November 2018, the Camp Fire devastated the mountain community of Paradise, CA. The burning of plastic pipes, wiring, construction materials, paint, and car batteries released toxic chemicals into the environment, contaminating the air, soil, and local waterways. Examples of toxins that were identified in the creeks and waterways in and around Paradise included pentachlorophenol (PCP), chrysene, and polyaromatic hydrocarbons. The effects of some of these chemicals on embryonic development, hematopoiesis (blood formation), and the immune system have not been thoroughly studied. Defining safe levels and the long-term effects of exposure is imperative to understanding and mitigating potential negative future outcomes. To perform these studies, we utilized zebrafish (Danio rerio), a commonly used vertebrate model system to study development. We observed the adverse effects of PCP on the development of zebrafish by using fluorescence microscopy, and saw that increased concentrations of PCP decreased the numbers of normal red blood cells and myeloid cells. Additionally, we observed that animal survival decreased in response to increasing concentrations of PCP. Furthermore, the prevalence of characteristic physical deformities such as tail curvature were greater in the treatment groups. Lastly, runx1, cmyb, and cd41 expression was reduced in fish treated with PCP. These results suggest that PCP has a previously underappreciated effect on blood and immune cell development and future studies should be performed to determine the molecular mechanisms involved.

The organochlorine pesticides pentachlorophenol and dichlorodiphenyltrichloroethane increase secretion and production of interleukin 6 by human immune cells.

The environmental contaminants pentachlorophenol (PCP) and 4, 4'-dichlorodiphenyltrichloroethane (DDT) are detected in some human blood samples at levels as high as 5 µM (PCP) and 260 nM (DDT). Several cancers are associated with exposures to these contaminants. IL-6 is a pro-inflammatory cytokine that when dysregulated stimulates inflammatory diseases and tumor progression. Immune cells exposed to PCP at 0.05-5 µM and DDT at 0.025-2.5 µM showed increased secretion of IL-6 when the cell preparations contained either T lymphocytes or monocytes. Increased IL-6 secretion was due to PCP and DDT induced cellular production of the cytokine and was dependent on MAP kinase signaling pathways (in the case of PCP). Compound-induced increases in IL-6 production were in part due to increases in either the transcription of and/or stability of its mRNA. Thus, both PCP and DDT have the potential to produce chronic inflammation by stimulating production of IL-6 by immune cells.

Hepatoprotective effects of the n-butanol extract from Perralderia coronopifolia Coss. against PCP-induced toxicity in Wistar albino rats.

In the present study, in vivo antioxidant properties of the n-butanol extract obtained from aerial parts of Perralderia coronopifolia were investigated in term of its hepatoprotective effect of female Wistar albino rats (n, 36; average age, 48 ± 5 days; weighing 150 ± 18 g) against PCP (pentachlorphenol)-induced toxicity. PCP (20 mg/kg b.w.) and plant extract (50 mg/kg b.w.) were administered daily by gavages for 2 weeks. Vitamin E (100 mg/kg b.w.) was given intraperitoneally as a positive control. Lipid peroxidation (LPO) levels, reduced glutathione (GSH) levels, and glutathione peroxidase (GPx) activities were evaluated in liver homogenates. While, aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol, and triglyceride parameters were analyzed in serums. The liver fragments were observed using light microscopy. Experimental results exhibited that PCP-treated group has a significant increase in the liver lipid peroxidation (LPO) levels of animals while decreased in plant extract-treated group. In addition, PCP caused significant decreases in glutathione peroxidase (GPx) activities and reduced glutathione (GSH) levels. Moreover, PCP induced hepatotoxicity by increasing serum transaminase enzymes, cholesterol, and triglyceride levels. While, these levels were restored to control value in animals treated with plant extract. The regularized levels of LPO, GSH, cholesterol, triglyceride, transaminase enzymes, and GPx activities revealed the antioxidant properties of the extract plant as well as of the vitamin E. The histological study showed the hepatoprotective effect of our extracts against PCP-induced acute intoxication, protecting the hepatic architecture and decreasing the functional and structural alterations of the liver. The plant extract had high antioxidant potential and completely prevented the toxic effect of PCP on the above of liver and serum parameters.

Cytotoxic activity of pentachlorophenol and its active metabolites in SH-SY5Y neuroblastoma cells.

As knowledge regarding mechanisms of pentachlorophenol (PCP) toxicity in neuronal cell lines is limited, the aim of the study was to evaluate the effects of PCP and its active metabolites, tetrachloro-1,4-benzoquinone (TCBQ) and tetrachlorohydroquinone (TCHQ) in human neuroblastoma SH-SY5Y cells. All compounds induced cytotoxic effects in time- and dose-dependent manners, and resulted in differential modes of cell death. Reduced mitochondrial membrane potential (Δá´ªM) and oxidative damage lead to apoptosis and necrosis following TCBQ and PCP exposure, respectively. Time-dependent investigations revealed transient Δá´ªM recovery in TCHQ exposed cells, and redox stress. Sufficient Δá´ªM recovery allowed apoptosis completion in TCHQ exposed cells, whereas overwhelming metabolic and oxidative stress saw a conversion from apoptotic to necrotic-like cell death. The onset of mitochondrial dysfunction preceded that of redox damage for all compounds, indicating that oxidative damage is secondary to Δá´ªM insult. Cytotoxic events were further linked to cell cycle. S phase and G2/M blocks were observed after 12 h exposure to TCBQ and TCHQ, respectively, while a G1 block occurred after 24 h exposure to PCP. This study provides new insight regarding time-dependant toxic effects of PCP and its metabolites in human neuronal cells.

Exposures to the environmental contaminants pentachlorophenol and dichlorodiphenyltrichloroethane increase production of the proinflammatory cytokine, interleukin-1ß, in human immune cells.

Pentachlorophenol (PCP) and dichlorodiphenyltrichloroethane (DDT) are organochlorine environmental contaminants found in human blood at very significant levels (as high as 5 µm for PCP and 260 nm for DDT). Cancers of the blood (lymphoma and myeloma) and kidney as well as others have been associated with exposure to these contaminants. Interleukin (IL)-1ß is a proinflammatory cytokine and is involved in stimulating cell proliferation. High levels of IL-1ß are associated with inflammatory diseases and tumor progression. Previous studies showed that PCP and DDT at certain concentrations were able to stimulate secretion of IL-1ß. This study shows that the increased secretion of IL-1ß seen with both contaminants is due to compound-induced increases in the production of this cytokine. Increased production began within 6 hours of exposure to PCP and continued to increase up to 24 hours. DDT-induced stimulation of IL-1ß appeared to be maximal after 6 hours of exposure and then diminished by 24 hours. The increases seen in IL-1ß production stimulated by PCP appear to be at least partially due to compound-induced increases in IL-1ß mRNA. Although DDT caused increased production of IL-1ß, it did not appear to cause consistent increases in its mRNA. PCP- and DDT-induced increases in IL-1ß production were dependent primarily on the p38 mitogen-activated protein kinase pathway. These results indicate that both PCP and DDT are able to increase IL-1ß production in a p38 mitogen-activated protein kinase-dependent manner, which may have the potential to influence chronic inflammation.

Maternal pentachlorophenol exposure induces developmental toxicity mediated by autophagy on pregnancy mice.

Pentachlorophenol (PCP) is often used as chlorinated hydrocarbon herbicides and insecticides, which has been suggested that toxicity of carcinogenic effect, teratogenic effect and reproductive system. However, there was still precious known about the underlying molecular mechanism of PCP on mammalian early development. To explore the developmental toxicity of PCP and its potential mechanism, pregnancy ICR mice except controls were exposed to PCP (0.02, 0.2 or 2 mg/kg) during gestation day (GD) 0.5 to GD8.5 in this study. We found that the fetal loss rate was increased and placental chorionic villi structure was disorder in hematoxylin-eosin staining (HE) on GD16.5. Meanwhile, autophagosomes were observed in chorionic villi through Transmission Electron Microscope (TEM). Moreover, the mRNA and/or protein expression of P62, LC3-ІІ/LC3-І and Beclin1 were increased in placenta, indicating the occurrence of autophagy. Then, to further explore the autophagy mechanism, microRNA (miR)-30a-5p, an expression inhibitor of Beclin1, was predicted through bioinformatics predictions and RT-PCR, and it was reduced in PCP-treated mice. Transfection and luciferase reporter gene test were used to verify the interaction between Beclin1 and miR-30a-5p. These results firstly indicate that, PCP exposure could downregulate the expression of miR-30a-5p, and then induced autophagy through upregulation of Beclin1 to result in fetal loss. Our study laid a foundation for understanding the PCP developmental toxicity through autophagy.

The Critical Role of X Chromosome-Linked Inhibitor of Apoptosis (XIAP) in Differential Synergism Induced by Pentachlorophenol and Copper-1,10-Phenanthroline Complex in Normal and Cancer Liver Cells.

Chemical pollutants often co-occur and can interact to cause unexpected combined toxic effects. Both pentachlorophenol (PCP) and copper-1,10-phenanthroline [Cu(OP)2], used as wood preservatives, coexist in fluids and tissues of ordinary population. Our previous studies demonstrate that a combination of subtoxic PCP and Cu(OP)2 causes synergistic toxicity on Escherichia coli and hepatocarcinoma cells. However, it is not clear whether this effect also occurs in normal hepatocytes; and if so, what are the differences as compared with the hepatocarcinoma cells. We demonstrate that the combination of low-toxic PCP and Cu(OP)2 (0-1.6 µM; PCP/Cu(OP)2 molar ratio: 2:1) induces a concentration-dependent intracellular copper accumulation, apoptosis, caspase-3/9 activation, depolarization of mitochondrial membrane potential, and oxidative stress (reactive oxygen species increasing and glutathione/oxidized glutathione ratio decreasing) in both normal hepatocytes HL-7702 and hepatocarcinoma HepG2 cells. However, HepG2 cells are more susceptible to the above molecular events as compared with HL-7702 cells. Further data reveal that PCP/Cu(OP)2 markedly decreases X chromosome-linked inhibitor of apoptosis (XIAP), p-ERK-1/2, and p-JNK protein expression in HepG2, but not HL-7702. Overexpression of XIAP gene in HepG2 significantly blocks PCP/Cu(OP)2-induced cytotoxicity, caspase activity, apoptosis, ROS accumulation, and antioxidant genes expression. These results suggest that the combination of low-toxic PCP and Cu(OP)2 preferentially induce synergistic cytotoxicity in human hepatocarcinoma cells by XIAP-ROS-apoptosis pathway, compared with the normal hepatocytes. The present data not only confirm the synergistic toxicity of PCP/Cu(OP)2 combination in normal liver cells, but also suggest a possible opportunity in developing new therapeutic approaches for liver cancer by sensitizing cancer cells to chemotherapy.

Atypical Gasdermin D and Mixed Lineage Kinase Domain-like Protein Leakage Aggravates Tetrachlorobenzoquinone-Induced Nod-like Receptor Protein 3 Inflammasome Activation.

Our previous study showed that tetrachlorobenzoquinone (TCBQ) mediated the activation of Nod-like receptor protein 3 (NLRP3) inflammasome, which involves K+ efflux, reactive oxygen species (ROS) production, and mitochondrial DNA damage. In addition, TCBQ down-regulates NLRP3 ubiquitination and promotes the activation of NLRP3 inflammasome. However, the induction of NLRP3 inflammasome by atypical pathways has not yet been characterized. Using human umbilical vein endothelial cells (HUVEC), we discovered that TCBQ activates caspase 1/4/5 and cleaves gasdermin D (GSDMD) into N-terminal and C-terminal cleavage products. In parallel, TCBQ also activates receptor interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like protein (MLKL) signaling pathways. The N-terminal fragments of GSDMD and MLKL translocate from cytoplasm to cell membrane and form oligomers and membrane pores on the cell membrane. The formation of membrane pores not only promotes the extracellular secretion of interleukin 1 beta (IL-1ß) but also affects cellular ion homeostasis, in particular promotes K+ outflow, which further activates NLRP3 inflammasome and aggravates cellular inflammation. These results indicated that GSDMD and MLKL play important roles in TCBQ-induced endothelial pro-inflammatory responses, which may point to potential therapeutic approaches for TCBQ-mediated toxicity.

Toxic effects of pentachlorophenol and 2,2',4,4'-tetrabromodiphenyl ether on two generations of Folsomia candida.

The standard Folsomia candida test (ISO 11267), in which only the survival and reproduction of the parental generation (F0) were determined, is insufficient to assess the toxicity of chemicals, like endocrine disrupting chemicals (EDCs), since the effects of EDCs could last for several generations and sometimes can be transgenerational. It's necessary to assess the effects on subsequent generations to address the long-term consequences of these chemicals exposure. In this study, the effects of pentachlorophenol (PCP) and 2,2',4,4'-tetrabromodiphenyl (BDE47) were assessed on F0 and the first filial generation (F1) of F. candida after 28-day or 10-day exposure of F0. In the 28-day exposure method, F0 was exposed to PCP or BD47 for 28 days and F1 was exposed for about 21 days. In the 10-day exposure method, F0 was exposed for 10 days and F1 was not exposed. The F. candida reproduction of F0 and F1 can be assessed in both methods, while transgenerational effects can further be evaluated in the 10-day exposure method. The numbers of F1 and F2 (second filial generation) juveniles in the 28-day exposure method and F1 juveniles in the 10-day exposure method decreased significantly for the PCP treatment. For BDE47, only the number of F1 juveniles in the 28-day exposure method significantly decreased. The EC50 values of F0 reproduction (the number of F1 juveniles) in the 28-day exposure method were 89 and 306 mg/kg dry soil for PCP and BDE47, respectively. Results suggested that PCP could affect F. candida egg hatching or juvenile survival and adult reproductive capacity, while BDE47 was more likely to affect egg hatchability or juvenile survival rather than adult reproductive capacity. It also indicated that F. candida exposed to PCP or BDE47 could recover in clean soil. Transgenerational effects were not observed for neither PCP nor BDE47 in this study.

Isolation and characterization of two glutathione S-transferases from freshwater bivalve Anodonta woodiana: Chronic effects of pentachlorophenol on gene expression profiles.

Glutathione S-transferases (GST) play a prominent role in protecting cells against oxidative stress. Our previous study showed that the reactive oxygen species (ROS) generated from pentachlorophenol (PCP) could cause an acute impact on freshwater bivalve Anodonta Woodiana, but its chronic toxicity remain unclear. In order to investigate the chronic effect of PCP, clams A. Woodiana were randomly grouped into PCP treated group in which animals were administrated with 13.9 µg/L concentrations of PCP, and control group those with similar volume dimethyl sulfoxide. In addition, two complete GST sequences were isolated from A. Woodianaa and respectively named AwGST1 and AwGST2. The full-length cDNA of AwGST1 was consisted of a 5' untranslated region (UTR) of 132 bp, a 3' UTR of 80 bp and an open reading frame (ORF) of 609 bp encoding a polypeptide of 203 amino acids. The full-length cDNA of AwGST2 contained a 5' UTR of 57 bp, a 3' UTR of 291 bp and an ORF of 678 bp encoding a polypeptide of 226 amino acids. The constitutive expression levels of AwGST1 and AwGST2 were examined in different tissues including foot, mantle, adductor muscle, heart, hepatopancreas, hemocytes and gill. Administration of PCP could result in a significant increase of AwGST1 and AwGST2 expression in the hepatopancreas, gill and hemocytes. In the hepatopancreas, AwGST1 mRNA levels of PCP treated group increased more than 28.73% at day 1, then 70.37% (P < 0.05) at day 3, reach to 6.64 times (P < 0.01) at day 15 in contrasted with that of control group. AwGST2 increased more 18.18%, 82.88% (P < 0.05) and 2.43 times (P < 0.01) at day 1, 3 and 15, respectively. In the gill, AwGST1 expression showed a significant up-regulation in the PCP treated group during experiment observed compared with that of control group, mRNA level of AwGST2 increased more than 1.44 times (P < 0.05). In addition, expressions of AwGST1 and AwGST2 were significantly induced after PCP treatment in the hemocytes. These results indicated that up-regulations of AwGST1 and AwGST2 expression in bivalve A. woodiana are contribute to against oxidative stress derived from PCP treatment during experiment observed.

The association of cancer risks with pentachlorophenol exposure: Focusing on community population in the areas along certain section of Yangtze River in China.

Pentachlorophenol (PCP) was used in large quantities, and mainly for killing the intermediate host snails of schistosome in China, thereby resulting in ubiquitous PCP residue in the environment. However, studies considering the carcinogenicity of PCP for humans mainly focused on occupational workers, and the actual carcinogenicity of PCP for general population is uncertain. To investigate the association between cancer risks and PCP exposure in a community population, an ecological study was conducted in three contaminated areas along the Yangtze River. Standardized rate ratio (SRR) was calculated to represent the risk of cancer incidence, by using incidence in the low PCP exposure category as the reference group. A total of 15,962 cancer records were collected, and 76 water samples and 213 urine samples in three areas were examined. Our findings suggested that compared with the low PCP group, the high PCP group had significantly excessive incidences of various cancers related to different organs including lymph (SRR = 19.44, 95% CI = 15.00-25.19), blood (SRR = 17.24, 95% CI = 12.92-23.01), nasopharynx (SRR = 3.97, 95% CI = 3.75-4.21), gallbladder (SRR = 3.46, 95% CI = 3.09-3.87), pancreas (SRR = 3.41, 95% CI = 3.07-3.79), respiratory system (SRR = 3.41, 95% CI = 3.27-3.57) and liver (SRR = 3.31, 95% CI = 3.09-3.56). Taken together, our present study provides evidence that general community population exposed to high level of PCP exhibits a broader spectrum of increased cancer risks as compared to occupational groups.

Exposures to the environmental toxicants pentachlorophenol (PCP) and dichlorodiphenyltrichloroethane (DDT) modify secretion of interleukin 1-beta (IL-1ß) from human immune cells.

Pentachlorophenol (PCP) and Dichlorodiphenyltrichloroethane (DDT) are environmental contaminants found in human blood. Previous studies have shown that PCP and DDT inhibit the lytic function of highly purified human natural killer (NK) lymphocytes and decrease the expression of several surface proteins on NK cells. Interleukin-1 ßeta (IL-1ß) is a cytokine produced by lymphocytes and monocytes, and anything that elevates its levels inappropriately can lead to chronic inflammation, which among other consequences can increase tumor development and invasiveness. Here, PCP and DDT were examined for their ability to alter secretion of IL-1ß from immune cell preparations of various complexity: NK cells; monocyte-depleted (MD) peripheral blood mononuclear cells (PBMCS); and PBMCs. Cells were exposed to concentrations of PCP ranging from 5 to 0.05 µM and DDT concentrations of 2.5-0.025 µM for 24, 48 h, and 6 days. Results showed that both PCP and DDT increased IL-1ß secretion from all of the immune cell preparations. The specific concentrations of PCP and DDT that increased IL-1ß secretion varied by donor. Immune cells from all donors showed compound-induced increases in IL-1ß secretion at one or more concentration at one or more length of exposure. The mechanism of PCP stimulation of IL1-ß secretion was also addressed, and it appears that the MAPKs, ERK1/2 and p38, may be utilized by PCP to stimulate secretion of IL-1ß.

A miniaturized electrochemical toxicity biosensor based on graphene oxide quantum dots/carboxylated carbon nanotubes for assessment of priority pollutants.

The study presented a sensitive and miniaturized cell-based electrochemical biosensor to assess the toxicity of priority pollutants in the aquatic environment. Human hepatoma (HepG2) cells were used as the biological recognition agent to measure the changes of electrochemical signals and reflect the cell viability. The graphene oxide quantum dots/carboxylated carbon nanotubes hybrid was developed in a facile and green way. Based on the hybrid composite modified pencil graphite electrode, the cell culture and detection vessel was miniaturized to a 96-well plate instead of the traditional culture dish. In addition, three sensitive electrochemical signals attributed to guanine/xanthine, adenine, and hypoxanthine were detected simultaneously. The biosensor was used to evaluate the toxicity of six priority pollutants, including Cd, Hg, Pb, 2,4-dinitrophenol, 2,4,6-trichlorophenol, and pentachlorophenol. The 24h IC50 values obtained by the electrochemical biosensor were lower than those of conventional MTT assay, suggesting the enhanced sensitivity of the electrochemical assay towards heavy metals and phenols. This platform enables the label-free and sensitive detection of cell physiological status with multi-parameters and constitutes a promising approach for toxicity detection of pollutants. It makes possible for automatical and high-throughput analysis on nucleotide catabolism, which may be critical for life science and toxicology.