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Jelena Marković, Milena Stošić, Danijela Kojić, Milica Matavulj
Oxidative stress is one of the principle mechanism of acrylamide-induced toxicity. Acrylamide is metabolized by cytochrome P450 2E1 (CYP2E1) to glycidamide or by direct conjugation with glutathione. Bearing in mind that up to now the effects of acrylamide on oxidative stress status and CYP2E1 level in endocrine pancreas have not been studied we performed qualitative and quantitative immunohistochemical evaluation of inducible nitric oxide synthase (iNOS), superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), catalase (CAT) and CYP2E1 expression in islets of Langerhans of rats subchronically treated with 25 or 50mg/kg bw of acrylamide...
December 7, 2017: Acta Histochemica
Pei Wu, Li Tian, Xiao-Qiu Zhou, Wei-Dan Jiang, Yang Liu, Jun Jiang, Fei Xie, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Juan Yang, Yong-An Zhang, He-Qun Shi, Lin Feng
This study evaluated the effect of dietary sodium butyrate (SB) supplementation on the intestinal physical barrier function of young grass carp (Ctenopharyngodon idella). The fish were fed one powdery sodium butyrate (PSB) diet (1000.0 mg kg-1 diet) and five graded levels of microencapsulated sodium butyrate (MSB) diets: 0.0 (control), 500.0, 1000.0, 1500.0 and 2000.0 mg kg-1 diet for 60 days. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila to explore the effect of SB supplementation on intestinal physical barrier function and the potential mechanisms in fish...
December 5, 2017: Fish & Shellfish Immunology
Octavio Jiménez-Garza, Liqiong Guo, Hyang-Min Byun, Mariella Carrieri, Giovanni Battista Bartolucci, Briscia Socorro Barrón-Vivanco, Andrea A Baccarelli
Occupational exposure to volatile organic compounds (VOCs) may cause hematopoietic malignancy, either by single exposure to benzene or possibly due to a concomitant exposure to several VOCs. Since oxidative stress, inflammation and DNA repair pathways are closely involved in cancer development, the effect of VOC exposure on expression of proteins involved in these pathways has been studied, but epigenetic changes have not been well described. Here, DNA methylation status following occupational exposure to a VOC mixture was assessed by bisulfite sequencing of the promoter regions of seven genes involved in the mentioned pathways...
December 4, 2017: Toxicology and Applied Pharmacology
Lukas Vrba, Bernard W Futscher
Cancer-specific DNA methylation from the tumor derived fraction of cell free DNA found in blood samples could be used for minimally invasive detection and monitoring of cancer. The knowledge of marker regions with cancer-specific DNA methylation is necessary to the success of such a process. We analyzed the largest cancer DNA methylation dataset available-TCGA Illumina HumanMethylation450 data with over 8,500 tumors-in order to find cancer-specific DNA methylation markers for most common human cancers. First, we identified differentially methylated regions for individual cancer types and those were further filtered against data from normal tissues to obtain marker regions with cancer-specific methylation, resulting in a total of 1,250 hypermethylated and 584 hypomethylated marker CpGs...
December 7, 2017: Epigenetics: Official Journal of the DNA Methylation Society
Stine Dam Henriksen, Poul Henning Madsen, Anders Christian Larsen, Martin Berg Johansen, Inge Søkilde Pedersen, Henrik Krarup, Ole Thorlacius-Ussing
Introduction: Few prognostic biomarkers are available for pancreatic cancer. The aim of this study is to examine the correlation between the survival of pancreatic adenocarcinoma patients and hypermethylated genes in plasma-derived cell-free DNA. Methods: Consecutive patients with pancreatic adenocarcinoma were prospectively included and staged according to the TNM classification. Methylation-specific PCR of 28 genes was conducted. A survival prediction model independent of cancer stage and stage-specific survival prediction models were developed by multivariable Cox regression analysis using backward stepwise selection...
November 7, 2017: Oncotarget
Marc Ansari, Patricia Huezo-Diaz Curtis, Chakradhara Rao S Uppugunduri, Mohammed Aziz Rezgui, Tiago Nava, Vid Mlakar, Laurence Lesne, Yves Théoret, Yves Chalandon, Lee L Dupuis, Tao Schechter, Imke H Bartelink, Jaap J Boelens, Robbert Bredius, Jean-Hugues Dalle, Saba Azarnoush, Petr Sedlacek, Victor Lewis, Martin Champagne, Christina Peters, Henrique Bittencourt, Maja Krajinovic
Busulfan (BU) dose adjustment following therapeutic drug monitoring contributes to better outcome of hematopoietic stem cell transplantation (HSCT). Further improvement could be achieved through genotype-guided BU dose adjustments. To investigate this aspect, polymorphism within glutathione S transferase genes were assessed. Particularly, promoter haplotypes of the glutathione S transferase A1 (GSTA1) were evaluated in vitro, with reporter gene assays and clinically, in a pediatric multi-center study (N =138) through association with BU pharmacokinetics (PK) and clinical outcomes...
October 31, 2017: Oncotarget
K Bolelli, Y Musdal, E Aki-Yalcin, B Mannervik, I Yalcin
Human GSTP1-1 is one of the most important proteins, which overexpresses in a large number of human tumours and is involved in the development of resistance to several anticancer drugs. So, it has become an important target in cancer treatment. In this study, 12 benzothiazole derivatives were synthesized and screened for their in vitro inhibitory activity for hGSTP1-1. Among these compounds, two of them (compounds #2 and #5) have been found to be the leads when compared with the reference drug etoposide. In order to analyse the structure-activity relationships (SARs) and to investigate the binding side interactions of the observed lead compounds, a HipHop pharmacophore model was generated and the molecular docking studies were performed by using CDocker method...
November 2017: SAR and QSAR in Environmental Research
Mohamad Amin Nourozi, Masoud Neghab, Javad Tavakkoly Bazzaz, Saharnaz Nejat, Yaser Mansoori, Seyed Jamaleddin Shahtaheri
Occupational exposure to benzene has been associated with leukemia, anemia, leukopenia, and thrombocytopenia. Genetic susceptibility to benzene toxicity in humans may be related to variations in benzene metabolizing genes. The main objective of this study was to ascertain whether polymorphism of GSTP1, GSTM1, GSTT1 and CYP2E1 genes might influence susceptibility to the adverse effects of benzene among employees of a petrochemical plant. In this cross-sectional study, 124 employees of a petrochemical plant who had been occupationally exposed to benzene and had one or more abnormal hematological parameter (cases) and 184 subjects with a similar exposure scenario, free from any abnormal hematological parameters (referent) were studied...
December 4, 2017: Archives of Toxicology
Chandra Kant Sharma, Monika Sharma, Kanika Prasad
Vitiligo is a condition of the skin distinguished by hypo-pigmentation. Etiology of this disorder is unknown, and several theories and mechanisms have been hypothesized. The inflammatory response in vitiligo is thought to be mediated by polymorphism in genes such as FOXP3, ACE, APE, GSTP1, TLR, SOD, CTLA-4, TAP/LMP gene cluster, etc. Theories including reactive oxygen species model, Nrf2-antioxidant response element (ARE) pathway, WNT pathway, tyrosinase activity, biochemical, molecular, and cellular alterations have been hypothesized to explain vitiligo pathogenesis...
2017: Critical Reviews in Eukaryotic Gene Expression
Catherine L Callahan, Matthew R Bonner, Jing Nie, Daikwon Han, Youjin Wang, Meng-Hua Tao, Peter G Shields, Catalin Marian, Kevin H Eng, Maurizio Trevisan, Jan Beyea, Jo L Freudenheim
BACKGROUND: We previously reported increased risk of breast cancer associated with early life exposure to two measures of air pollution exposure, total suspended particulates (TSP) and traffic emissions (TE), possible proxies for exposure to polycyclic aromatic hydrocarbons (PAHs). Exposure to PAHs has been shown to be associated with aberrant patterns of DNA methylation in peripheral blood of healthy individuals. Exposure to PAHs and methylation in breast tumor tissue has received little attention...
November 30, 2017: Environmental Research
Xiaohong Yang, Wenyi Liu, Hui Lin, Hui Zeng, Renping Zhang, Chaowen Pu, Lingqiao Wang, Chuanfen Zheng, Yao Tan, Yang Luo, Xiaobin Feng, Yingqiao Tian, Guosheng Xiao, Jia Wang, Yujing Huang, Jiaohua Luo, Zhiqun Qiu, Ji-An Chen, Liping Wu, Lixiong He, Weiqun Shu
AFB1 and MC-LR are two major environmental risk factors for liver damage worldwide, especially in warm and humid areas, but there are individual differences in health response of the toxin-exposed populations. Therefore, we intended to identify the susceptible genes in transport and metabolic process of AFB1 and MC-LR and find their effects on liver damage. We selected eight related SNPs that may affect liver damage outcomes in AFB1 and MC-LR exposed persons, and enrolled 475 cases with liver damage and 475 controls of healthy people in rural areas of China...
November 23, 2017: Scientific Reports
M Wang, S Ji, G Shao, J Zhang, K Zhao, Z Wang, A Wu
PURPOSE: Exosomes are gradually detected as an indicator for diagnosis and prognosis of breast cancer in clinic and a systematic review was conducted. METHODS: A search for clinical studies published before July 1, 2017 was performed. Methods of exosome purification and identification from all studies were extracted. For diagnosis evaluation, the comparison of exosome biomarkers expression between breast cancer patients and healthy women was obtained; for prognosis prediction, the correlation between exosome biomarkers expression and chemotherapy resistance, overall survival (OS), disease-free survival (DFS), recurrence and metastasis of breast cancer was also extracted...
November 15, 2017: Clinical & Translational Oncology
Ang Li, Chuan Yang, Min Hu
OBJECTIVE: To determine the expression level of GSTP1 in colon tumor tissues at different stages and the effects of GSTP1 expression on colon tumor cells,and to identify miR that regulate the expression of GSTP1. METHODS: Realtime PCR and western blot were used to detect the expression level of GSTP1 in colon tumor tissues. pcDNA3.1GSTP1 was constructed and transfected into human colon tumor cell line HCT116. The apoptosis rate and viability of HCT116 were measured...
September 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
Minlan Yang, Yanru Li, Xiangfeng Shen, Yang Ruan, Yan Lu, Xiangshu Jin, Peiye Song, Yantong Guo, Xiaoli Zhang, Huinan Qu, Yijia Shao, Chengshi Quan
BACKGROUND: Claudin-6 (CLDN6), a member of CLDN family and a key component of tight junction, has been reported to function as a tumor suppressor in breast cancer. However, whether CLDN6 plays any role in breast cancer chemoresistance remains unclear. In this study, we investigated the role of CLDN6 in the acquisition of chemoresistance in breast cancer cells. METHODS: We manipulated the expression of CLDN6 in MCF-7 and MCF-7/MDR cells with lv-CLDN6 and CLDN6-shRNA and investigated whether CLDN6 manipulation lead to different susceptibilities to several chemotherapeutic agents in these cells...
November 7, 2017: Journal of Experimental & Clinical Cancer Research: CR
Sharon Howell, Kwesi Marshall, Marvin Reid, Norma McFarlane-Anderson, Colin McKenzie
OBJECTIVES: To explore putative associations between specific variants in either the glutathione S-transferase (GST), haptoglobin (HP), or uridine 5'-diphospho-glucuronosyltransferase 1A1 (UGT1A1) genes and clinically important phenotypes in sickle cell anaemia (HbSS). METHODS: Three hundred and seventy-one HbSS participants were recruited from the Sickle Cell Clinic of the Sickle Cell Unit at the University of the West Indies, Kingston, Jamaica. Markers within four GST superfamily genes, the HP gene, and the UGT1A1 gene were analyzed using PCR-based assays...
November 7, 2017: European Journal of Haematology
Xiaoran Duan, Yongli Yang, Sihua Wang, Xiaolei Feng, Tuanwei Wang, Pengpeng Wang, Suxiang Liu, Lei Li, Guoyu Li, Wu Yao, Liuxin Cui, Wei Wang
Purpose: This study aimed to explore the effects of genetic polymorphisms in metabolic enzymes on relative telomere length changes and explore the mechanism of canceration induced by omethoate. Materials and Methods: 180 long-term omethoate-exposed workers and 115 healthy controls were recruited. Real-time PCR method was applied to determine the relative telomere length in peripheral blood leukocytes DNA, and Six polymorphic loci of GSTT1(+/-), GSTM1(+/-), GSTP1 rs1695, CYP2E1 rs6413432, CYP2E1 rs3813867 and PON2 rs12026 were detected by polymerase chain reaction and restriction fragment length polymorphism method; Multiple linear regression was conducted to explore the effects of omethoate exposure and genetic polymorphisms on the telomere length...
October 6, 2017: Oncotarget
Zan Li, Jie Ding, Chunxia Chen, Jiayin Chang, Binghuan Huang, Zhirong Geng, Zhilin Wang
We developed a dual-target theranostic F671, which could exhibit synergetic anticancer effects for inhibiting the activities of glutathione S-transferase and the accumulation of hypoxia inducible factor-1α. F671 undergoes self-immolative cleavage when exposed to GSTP1-1 in live cancer cells, facilitating the visualization of molecule release and distribution, as well as confirming the autophagy-induced apoptosis.
November 16, 2017: Chemical Communications: Chem Comm
Iuliia Azarova, Olga Bushueva, Alexander Konoplya, Alexey Polonikov
BACKGROUND: A compromised defense against reactive oxygen species (ROS) is considered to play an important role in the pathogenesis of type 2 diabetes (T2D), therefore, genes encoding antioxidant defense enzymes may contribute to disease susceptibility. The present study investigated whether polymorphisms in the genes encoding glutathione S-transferase M1 (GSTM1), T1 (GSTT1) and P1 (GSTP1) jointly contribute to the risk of T2D. METHODS: A total of 1,120 unrelated Russian subjects, including 600 patients with T2D and 520 age- and sex-matched healthy subjects, were recruited for this study...
November 7, 2017: Journal of Diabetes
Jinfeng Wen, Tuo Zheng, Kefeng Hu, Chunxia Zhu, Lihua Guo, Guoliang Ye
Gene promoter methylation has been reported in gastric cancer (GC). However, the potential applications of blood-based gene promoter methylation as a noninvasive biomarker for GC detection remain to be evaluated. Hence, we performed this analysis to determine whether promoter methylation of 11 tumor-related genes could become a promising biomarker in blood samples in GC. We found that the cyclin-dependent kinase inhibitor 2A (p16), E-cadherin (CDH1), runt-related transcription factor 3 (RUNX3), human mutL homolog 1 (MLH1), RAS association domain family protein 1A (RASSF1A), cyclin-dependent kinase inhibitor 2B (p15), adenomatous polyposis coli (APC), Glutathione S-transferase P1 (GSTP1), TP53 dependent G2 arrest mediator candidate (Reprimo), and O6-methylguanine-DNAmethyl-transferase (MGMT) promoter methylation was notably higher in blood samples of patients with GC compared with non-tumor controls...
September 29, 2017: Oncotarget
Mirna Velki, Henriette Meyer-Alert, Thomas-Benjamin Seiler, Henner Hollert
The zebrafish as a test organism enables the investigation of effects on a wide range of biological levels from molecular level to the whole-organism level. The use of fish embryos represents an attractive model for studies aimed at understanding toxic mechanisms and the environmental risk assessment of chemicals. In the present study, a zebrafish (Danio rerio) in vivo model was employed in order to assess the effects of two commonly used pesticides, the insecticide diazinon and the herbicide diuron, on zebrafish early life stages...
October 28, 2017: Aquatic Toxicology
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