scholarly journals Assessment of androgenic response potential of effluents using in vitro and in vivo methods

2021 ◽  
Author(s):  
Emil Bandelj
Keyword(s):  
Androgen Receptor ◽  
New Zealand ◽  
Sewage Treatment Plant ◽  
Treatment Plant ◽  
Pulp Mill ◽  
Microbial Conversion ◽  
Aromatase Inhibition ◽  
In Vitro Methods

The androgenic potential of a New Zealand pulp mill effluent (PME) and a Canadian PME was assessed along with a New Zealand sewage treatment plant effluent (STP) using a combination of in vivo and in vitro methods. The in vitro methods included: (1) a fish-based androgen receptor binding assay, (2) a fish-based aromatase inhibition activity assay, and (3) an analysis of gonadal sex steroid levels in exposed female mosquitofish ( Gambusia affinis ) ovaries by radioimmunoassay. The in vivo method included a quantifiable analysis of anal fin ray length for female mosquitofish exposed to the effluents. Effluent extracts for the Canadian PME and New Zealand STP were found to have low in vitro androgenic potential compared to upstream reference extracts. All effluent extracts (Canadian PME, New Zealand PME and STP) showed a low degree of in vitro aromatase inhibition potential compared to upstream reference extracts. In vivo analysis showed no androgenic potential of the New Zealand PME and STP. The in vitro androgen receptor assay and in vivo mosquitofish bioassay did show androgenic responses for androstenedione (AD) and 1,4-androsta-diene-3,17-dione (ADD), which are two products of the microbial conversion of β-sitosterol (a plant sterol commonly found in PME) by Mycobacterium smegmatis . Also, the potential of the mosquitofish bioassay to determine anti-androgenic effects in effluents was demonstrated.

scholarly journals Assessment of androgenic response potential of effluents using in vitro and in vivo methods

2021 ◽  
Author(s):  
Emil Bandelj
Keyword(s):  
Androgen Receptor ◽  
New Zealand ◽  
Sewage Treatment Plant ◽  
Treatment Plant ◽  
Pulp Mill ◽  
Microbial Conversion ◽  
Aromatase Inhibition ◽  
In Vitro Methods

The androgenic potential of a New Zealand pulp mill effluent (PME) and a Canadian PME was assessed along with a New Zealand sewage treatment plant effluent (STP) using a combination of in vivo and in vitro methods. The in vitro methods included: (1) a fish-based androgen receptor binding assay, (2) a fish-based aromatase inhibition activity assay, and (3) an analysis of gonadal sex steroid levels in exposed female mosquitofish ( Gambusia affinis ) ovaries by radioimmunoassay. The in vivo method included a quantifiable analysis of anal fin ray length for female mosquitofish exposed to the effluents. Effluent extracts for the Canadian PME and New Zealand STP were found to have low in vitro androgenic potential compared to upstream reference extracts. All effluent extracts (Canadian PME, New Zealand PME and STP) showed a low degree of in vitro aromatase inhibition potential compared to upstream reference extracts. In vivo analysis showed no androgenic potential of the New Zealand PME and STP. The in vitro androgen receptor assay and in vivo mosquitofish bioassay did show androgenic responses for androstenedione (AD) and 1,4-androsta-diene-3,17-dione (ADD), which are two products of the microbial conversion of β-sitosterol (a plant sterol commonly found in PME) by Mycobacterium smegmatis . Also, the potential of the mosquitofish bioassay to determine anti-androgenic effects in effluents was demonstrated.

Analysis of antidepressant properties of some Papaver species by in vivo and in vitro methods

Planta Medica ◽  
2015 ◽  
Vol 81 (16) ◽  
Author(s):  
OML Bayazeid ◽  
F Yalcin ◽  
M İlhan ◽  
H Karahan ◽  
E Kupeli-Akkol ◽  
...  
Keyword(s):  
In Vitro Methods

The Effects of Some Synthetic Compounds on In Vitro Fibrinolytic Activity Measured by Different Methods and the Relevance to Activity In Vivo

1972 ◽  
Vol 28 (03) ◽  
pp. 351-358
Author(s):  
A.J Baillie ◽  
A. K Sim
Keyword(s):  
Inhibitory Activity ◽  
Substrate Concentration ◽  
Fibrinolytic Activity ◽  
Synthetic Compounds ◽  
In Vitro Methods ◽  
Narrow Concentration Range

SummaryThe activity of several synthetic compounds, rated from good to poor (or inactive) fibrinolytic activators, has been assessed by two different commonly-used in vitro methods. Compounds shown to be active over a narrow concentration range in the hanging clot test were shown to be inhibitors of plasmin and trypsin in the casein-olytic test. The inhibitory activity of these compounds was shown to increase with increasing substrate concentration and apparent activity in the hanging clot test. Possible explanations and relevance of these observations are discussed.

scholarly journals Interrogation of gender disparity uncovers androgen receptor as the transcriptional activator for oncogenic miR-125b in gastric cancer

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Ben Liu ◽  
Meng Zhou ◽  
Xiangchun Li ◽  
Xining Zhang ◽  
Qinghua Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Androgen Receptor ◽  
Signaling Pathway ◽  
Gender Bias ◽  
Gender Disparity ◽  
Gene Set Enrichment Analysis ◽  
Cancer Type ◽  
Female Patients

AbstractThere is a male preponderance in gastric cancer (GC), which suggests a role of androgen and androgen receptor (AR). However, the mechanism of AR signaling in GC especially in female patients remains obscure. We sought to identify the AR signaling pathway that might be related to prognosis and examine the potential clinical utility of the AR antagonist for treatment. Deep learning and gene set enrichment analysis was used to identify potential critical factors associated with gender bias in GC (n = 1390). Gene expression profile analysis was performed to screen differentially expressed genes associated with AR expression in the Tianjin discovery set (n = 90) and TCGA validation set (n = 341). Predictors of survival were identified via lasso regression analyses and validated in the expanded Tianjin cohort (n = 373). In vitro and in vivo experiments were established to determine the drug effect. The GC gender bias was attributable to sex chromosome abnormalities and AR signaling dysregulation. The candidates for AR-related gene sets were screened, and AR combined with miR-125b was associated with poor prognosis, particularly among female patients. AR was confirmed to directly regulate miR-125b expression. AR-miR-125b signaling pathway inhibited apoptosis and promoted proliferation. AR antagonist, bicalutamide, exerted anti-tumor activities and induced apoptosis both in vitro and in vivo, using GC cell lines and female patient-derived xenograft (PDX) model. We have shed light on gender differences by revealing a hormone-regulated oncogenic signaling pathway in GC. Our preclinical studies suggest that AR is a potential therapeutic target for this deadly cancer type, especially in female patients.

In Vitro Toxicology Methods in Risk Assessment

1996 ◽  
Vol 24 (3) ◽  
pp. 325-331
Author(s):  
Iain F. H. Purchase
Keyword(s):  
Risk Assessment ◽  
Hazard Assessment ◽  
Human Health Risk ◽  
In Vitro Test ◽  
In Vitro Methods ◽  
New Concepts ◽  
Vitro Test

The title of this paper is challenging, because the question of how in vitro methods and results contribute to human health risk assessment is rarely considered. The process of risk assessment usually begins with hazard assessment, which provides a description of the inherent toxicological properties of the chemical. The next step is to assess the relevance of this to humans, i.e. the human hazard assessment. Finally, information on exposure is examined, and risk can then be assessed. In vitro methods have a limited, but important, role to play in risk assessment. The results can be used for classification and labelling; these are methods of controlling exposure, analogous to risk assessment, but without considering exposure. The Ames Salmonella test is the only in vitro method which is incorporated into regulations and used widely. Data from this test can, at best, lead to classification of a chemical with regard to genotoxicity, but cannot be used for classification and labelling on their own. Several in vitro test systems which assess the topical irritancy and corrosivity of chemicals have been reasonably well validated, and the results from these tests can be used for classification. The future development of in vitro methods is likely to be slow, as it depends on the development of new concepts and ideas. The in vivo methods which currently have reasonably developed in vitro alternatives will be the easiest to replace. The remaining in vivo methods, which provide toxicological information from repeated chronic dosing, with varied endpoints and by mechanisms which are not understood, will be more difficult to replace.

Case study in 21 st century ecotoxicology: using in vitro aromatase inhibition data to predict short term in vivo responses in adult female fish

2020 ◽  
Author(s):  
Daniel L. Villeneuve ◽  
Brett R. Blackwell ◽  
Jenna E. Cavallin ◽  
Wan‐Yun Cheng ◽  
David J. Feifarek ◽  
...  
Keyword(s):  
Adult Female ◽  
Female Fish ◽  
Aromatase Inhibition ◽  
Short Term ◽  
Inhibition Data

Studies of Metabolism Mediated Mutagenicity In Vitro

1990 ◽  
Vol 18 (1_part_1) ◽  
pp. 243-250
Author(s):  
Dag Jenssen ◽  
Lennart Romert
Keyword(s):  
Cell Lines ◽  
Biological Effects ◽  
Animal Experiments ◽  
Culture Technique ◽  
Organ Perfusion ◽  
Isolated Cells ◽  
Toxicological Effect ◽  
In Vitro Methods

To understand the cause of the biological effects of xenobiotic metabolism in mammals, investigators have traditionally performed animal experiments by comparing the results of biochemical methods, such as measurement of enzyme activity analysis of the metabolites produced, with the observed toxicological effect. This article deals with in vitro methods for genotoxicity combined with drug metabolising preparations at the organelle, cell or organ levels, as exemplified by microsome preparations, isolated cells/cell lines and organ perfusion systems, respectively. The advantage of some of these methods for studying metabolism-mediated mutagenicity is that the measured endpoint reflects not only the bioactivating phase I reactions, but also the detoxifying phase II reactions, and the transfer of the non-conjugated reactive metabolites to other cells and their ability to cause mutations in these cells. In vivo, all these events are important factors in the initiation of cancer. A mechanistic advantage of the methods for metabolism-mediated mutagenicity in vitro is that the relevance of the different steps in metabolism for the mutational events can seldom be investigated in an in vivo assay. Furthermore, human studies can easily be performed using the co-culture technique with isolated human cells or cell lines.

scholarly journals Antiproliferative Effect of Androgen Receptor Inhibition in Mesenchymal Stem-Like Triple-Negative Breast Cancer

2016 ◽  
Vol 38 (3) ◽  
pp. 1003-1014 ◽  
Author(s):  
Aiyu Zhu ◽  
Yan Li ◽  
Wei Song ◽  
Yumei Xu ◽  
Fang Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative

Background/Aims: Androgen receptor (AR), a steroid hormone receptor, has recently emerged as prognostic and treatment-predictive marker in breast cancer. Previous studies have shown that AR is widely expressed in up to one-third of triple-negative breast cancer (TNBC). However, the role of AR in TNBC is still not fully understood, especially in mesenchymal stem-like (MSL) TNBC cells. Methods: MSL TNBC MDA-MB-231 and Hs578T breast cancer cells were exposed to various concentration of agonist 5-α-dihydrotestosterone (DHT) or nonsteroidal antagonist bicalutamide or untreated. The effects of AR on cell viability and apoptosis were determined by MTT assay, cell counting, flow cytometry analysis and protein expression of p53, p73, p21 and Cyclin D1 were analyzed by western blotting. The bindings of AR to p73 and p21 promoter were detected by ChIP assay. MDA-MB-231 cells were transplanted into nude mice and the tumor growth curves were determined and expression of AR, p73 and p21 were detected by Immunohistochemistry (IHC) staining after treatment of DHT or bicalutamide. Results: We demonstrate that AR agonist DHT induces MSL TNBC breast cancer cells proliferation and inhibits apoptosis in vitro. Similarly, activated AR significantly increases viability of MDA-MB-231 xenografts in vivo. On the contrary, AR antagonist, bicalutamide, causes apoptosis and exerts inhibitory effects on the growth of breast cancer. Moreover, DHT-dependent activation of AR involves regulation in the cell cycle related genes, including p73, p21 and Cyclin D1. Further investigations indicate the modulation of AR on p73 and p21 mediated by direct binding of AR to their promoters, and DHT could make these binding more effectively. Conclusions: Our study demonstrates the tumorigenesis role of AR and the inhibitory effect of bicalutamide in AR-positive MSL TNBC both in vitro and in vivo, suggesting that AR inhibition could be a potential therapeutic approach for AR-positive TNBC patients.

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