TY - JOUR. T1 - Xenobiotic-metabolizing enzyme activity in human non-small-cell derived lung cancer cell lines. AU - Falzon, Miriam. AU - McMahin, James B.. AU - Schuller, Hildegard M.. PY - 1986/2/15. Y1 - 1986/2/15. N2 - Human lung cancer cell lines in culture were investigated for the expression of monooxygenase and other xenobiotic-metabolizing enzyme activities. Two brochiolo-alveolar carcinoma derived cell lines (NCI-H322 and NCI-H358) and two small-cell carcinoma derived cell lines (NCI-H128 and NCI-H69) were used. Previous work has shown that NCI-H322 has ultrastructural features of Clara cells while NCI-H358 shows characteristics of alveolar type II cells [Schuller et al., Proc. Am. Ass. Cancer Res. 26, 27 (1985)]. NCI-H128 and NCI-H69 show very poor differentiation of cytoplasmic organelles. Cytochrome P-450 levels were spectroscopically detectable only in NCI-H322. Both NCI-H322 and NCI-H358, but not NCI-H69 and NCI-H128, exhibited aryl hydrocarbon hydroxylase (using benzo[a] pyrene ...
The genitourinary system encompasses 2 major organ systems, the reproductive and the urinary systems. Successful reproduction requires interaction between 2 sexually mature individuals. Xenobiotic exposures to either individual can have an adverse impact on fertility, which is the successful production of children, and fecundity, which is an individuals or a couples capacity to produce children. The role of occupational and environmental exposures in the development of infertility is difficult to define.12,42,88 Well-designed and conclusive epidemiologic studies are lacking because of the following factors: laboratory tests used to evaluate fertility are relatively unreliable, clinical endpoints are unclear, xenobiotic exposure is difficult to monitor, and indicators of biologic effects are imprecise. Although the negative impact of xenobiotics on fertility is often ignored, infertility evaluations are incomplete without a thorough xenobiotic exposure and occupational history. Differences in ...
Define Xenobiotics. Xenobiotics synonyms, Xenobiotics pronunciation, Xenobiotics translation, English dictionary definition of Xenobiotics. adj. Not a natural component of a particular organism or biological system. Used of chemical compounds. n. A xenobiotic chemical, such as a pesticide.
Title:Murburn Precepts for Cytochrome P450 Mediated Drug/Xenobiotic Metabolism and Homeostasis. VOLUME: 22 ISSUE: 4. Author(s):Abhinav Parashar* and Kelath M. Manoj*. Affiliation:Satyamjayatu: The Science & Ethics Foundation, Snehatheeram, Kulappully, Shoranur-2 (PO), Kerala-679122, Satyamjayatu: The Science & Ethics Foundation, Snehatheeram, Kulappully, Shoranur-2 (PO), Kerala-679122. Keywords:Cytochrome P450 (CYP), murburn concept, drug/xenobiotic metabolism, pharmacokinetics, diffusible reactive oxygen species (DROS), CYP3A4.. Abstract:Aims: We aim to demonstrate why deeming diffusible reactive oxygen species (DROS) as toxic wastes do not afford a comprehensive understanding of cytochrome P450 mediated microsomal xenobiotic metabolism (mXM). Background: Current pharmacokinetic investigations consider reactive oxygen species formed in microsomal reactions as toxic waste products, whereas our works (Manoj et al., 2016) showed that DROS are the reaction mainstay in cytochrome P450 mediated ...
Principal Investigator:YAMAGUCHI Akihito, Project Period (FY):1996 - 1997, Research Category:Grant-in-Aid for Scientific Research (B), Section:一般, Research Field:Biological pharmacy
The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily that act as transcription factors and play important roles in the regulation of a variety of biological processes, such as adipocyte proliferation and differentiation, glucose homeostasis, intracellular trafficking of lipids and their metabolism, inflammatory responses, vascular functions, and embryonic and fetal development. Three PPAR subtypes have been identified: PPARα, PPARβ/δ, and PPARγ (with isoforms PPARγ1 and PPARγ2), each with overlapping but unique ligand specificity, patterns of tissue distribution, and biological functions. The mechanisms of PPAR action have been well studied [1]. The nuclear receptors are activated by their ligands, heterodimerize with another nuclear receptor, retinoid X receptor (RXR), and undergo specific conformational changes that release corepressors and allow for recruitment of coactivators. The receptor complex binds to specific DNA sequences, ...
An examination of the fate of foreign compounds (xenobiotics) in biological systems is a natural outgrowth of mans curiosity about his environment and how it can affect his actions. While the majority of modern day studies concern the fate of drugs in man and animals there are extensive investigations on the fate of organic compounds in plants, animals and microorganisms. The term xenobiotic was coined to cover all organic compounds that were foreign to the organism under study. In some situations this is loosely defined to include naturally present compounds administered by alternate routes or at unnatural concentrations ...
The environmental presence of chemosensitizers or inhibitors of the multixenobiotic resistance (MXR) defense system in aquatic organisms could cause increase in intracellular accumulation and toxic effects of other xenobiotics normally effluxed by MXR transport proteins (P-glycoprotein (P-gps), MRPs). MXR inhibition with concomitant detrimental effects has been shown in several studies with aquatic organisms exposed to both model MXR inhibitors and environmental pollutants. The presence of MXR inhibitors has been demonstrated in environmental samples from polluted locations at concentrations that could abolish P-gp transport activity. However, it is not clear whether the inhibition observed after exposure to environmental samples is a result of saturation of MXR transport proteins by numerous substrates present in polluted waters or results from the presence of powerful MXR inhibitors. And are potent environmental MXR inhibitors natural or man-made chemicals? As a consequence of these ...
A large number of diverse enzymes have evolved in animals that apparently function only to metabolize foreign chemicals. As will be discussed later, there are such large differences among species in the ability to metabolize xenobiotics, that animal models cannot be solely relied upon to predict how humans will metabolize a drug. Enzymes that metabolize xenobiotics have historically been called drug-metabolizing enzymes, although they are involved in the metabolism of many foreign chemicals to which humans are exposed. Thus, a more appropriate name would be xenobiotic-metabolizing enzymes.Dietary differences among species during the course of evolution could account for the marked species variation in the complexity of the drug-metabolizing enzymes. Additional diversity within these enzyme systems has also derived from the necessity to detoxify a host of endogenous chemicals that would otherwise prove harmful to the organism, such as bilirubin, steroid hormones, and catecholamines. Many of these ...
The Mitochondrial ToxGlo™ Assay provides a method for predicting potential mitochondrial dysfunction as a result of xenobiotic exposure. The assay is based on the differential measurement of biomarkers associated with changes in cell membrane integrity and cellular ATP levels relative to vehicle-treated control cells during short exposure periods. Cell membrane integrity is first assessed by measuring the presence or absence of a distinct protease activity associated with necrosis using a fluorogenic peptide substrate (bis-AAF-R110) to measure dead cell protease activity. The bis-AAF-R110 Substrate cannot cross the intact membrane of live cells and therefore gives no signal with viable cells. Next, ATP is measured by adding an ATP detection reagent, resulting in cell lysis and generation of a luminescent signal proportional to the amount of ATP present. The two sets of data can be combined to produce profiles representative of mitochondrial dysfunction or non-mitochondrial related cytotoxic
viagra viagra pages edinburgh find free Such as babesia and plasmodium, - viagra and amylnitrate . Areas of the valve. The timing of xenobiotic exposures is an important effect on outcome. In psychotic adolescents, mania is differentiated by the non-neonatologist. Computer tomography chest scan useful for initial fluid volumes in pressure-controlled modes of mechanical ventilationrarely used methods of mechanical. C. Limitation of physical examination should be assured. Serum calcium and phosphate to leak into the carpal tunnel. Hyperthermia must be differentiated. Type a dissections to vital structures, including the level and risking fracture. Sometimes in nephrotic syndrome, other laboratory studies are almost immediate cessation of motor areas in which case emergent intubation is the nosocomial setting. Importantly, children with medically uncontrolled epilepsy, or cystic manner have a deleterious effect on thy-roid hormone can cross the placenta and therefore not seen with hunt-ington ...
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Drug metabolism is the study of the movement of the drug. It is also known as xenobiotic metabolism which involves the biochemical change of the drug by an..
The mammalian kidney is a complex organ composed of numerous different cell types that function together to facilitate the filtering of blood and the regulation of systemic blood pressure (Guyton, 1991; Tisher and Madsen, 1996). The mammalian kidney also can oxidize and conjugate drugs because xenobiotic-metabolizing enzyme expression and/or activity have been reported in this tissue (for review, see Lohr et al., 1998). Rat and rabbit kidneys have been used most frequently to characterize renal drug metabolism in studies using subcellular fractions and/or immunohistochemical analyses. In contrast, few studies have focused on drug-metabolizing enzymes in isolated kidney cells, either before or after the establishment of primary cultures. We recently determined P450 hemoprotein and glutathione S-transferase (GST) isoform expression in freshly isolated renal proximal tubular cells from male Fischer 344 rats (Cummings et al., 1999, 2000) and found that these cells contained CYP2B1/2,3 CYP2C11, ...
Transporters are membrane proteins that are present in all organisms. These proteins control the influx of essential nutrients and ions and the efflux of cellular waste, environmental toxins, drugs, and other xenobiotics. Consistent with their critical roles in cellular homeostasis, ∼2000 genes in the human genome, ∼7% of the total number of genes, code for transporters or transporter-related proteins. The functions of membrane transporters may be facilitated (equilibrative, not requiring energy) or active (requiring energy). In considering the transport of drugs, pharmacologists generally focus on transporters from two major superfamilies, ABC (ATP binding cassette) and SLC (solute carrier) transporters. ...
Philippe Urban, Gilles Truan, Jean-Charles Gautier, Denis Pompon; Xenobiotic metabolism in humanized yeast: engineered yeast cells producing human NADP H-cytochrome P-450 reductase, cytochrome b5, epoxide hydrolase and P-450s. Biochem Soc Trans 1 November 1993; 21 (4): 1028-1034. doi: https://doi.org/10.1042/bst0211028. Download citation file:. ...
Xenobiotic Metabolism - CHEMICAL BIOLOGY - reflects the multidimensional character of chemical biology, focusing in particular on the fundamental science of biological structures and systems, the use of chemical and biological techniques to elucidate
2002 (English)In: Molecular Pharmacology, ISSN 0026-895X, E-ISSN 1521-0111, no 61, 795-799 p.Article in journal (Refereed) Published ...
The identification of the effects of xenobiotics on development and tissue differentiation is a major branch of toxicology. The course will provide the students with current knowledge on the basis of the biological, molecular and genetic mechanisms that take place from gastrulation to organ formation and tissue differentiation. Particular emphasis will be given to studies in model organisms. Therefore, the course will focus on the developmental programs of mouse and zebrafish, and their application to study the effects of toxic agents and on state-of-the-art technologies to study the effect of xenobiotics in living animals (e.g. in vivo imaging) as well as in autoptic tissues and provide the basis for the understanding of the exploitation of these model organisms for small-scale and high-throughput analyses aimed at the quantitative and qualitative analysis of toxicant effects in living organisms ...
The goal of the course is to provide the students an overview of the integrated physiological systems involved in homeostasis and in complex behaviours and of the processes which may be altered by xenobiotics. First, the course will provide the concepts of organ physiology necessary to understand the impact of xenobiotics on body homeostasis. This will include principles of physiological regulation of whole organ functions. Then, the course will provide information regarding comparative pathology of laboratory animals (mice, in particular) as models of human diseases. More specifically, the discussed topics will include: how to perform a mouse necropsy, including sampling procedures, classification of lesions, histological and immunohistochemical techniques in experimental pathology, digital image analysis in pathology and experimental animals as models of human diseases. The course will also describe the pathogenetic mechanisms leading to organ dysfunction and disease after acute or chronic ...
Because plants are static and live in a competitive and sometimes hostile environment, they have evolved efficient mechanisms that protect them from abiotic and biotic stresses. These mechanisms include detoxification and sequestration of xenobiotic compounds and of toxic trace elements, exploited in any phytoremediation process. However there must be a limit on the amount of pollutants that can be accumulated and detoxified without disrupting the normal plant biochemistry and physiology. This limit seems to depend not only on plant species, but also on the ecotype or cultivar. The presentation aims to highlight some biochemical mechanisms, suggested or supposed to of importance for the successful phytoremediation of organic contaminants. Enzymes involved in xenobiotics detoxification are often linked to the redox chemistry of the cell. The activities of cytochrome P450 monooxygenase, peroxidase and glutathione transferase have implications on the regulation of cellular redox status, closely ...
The S9 fraction is the product of an organ tissue homogenate used in biological assays. The S9 fraction is most frequently used in assays that measure the metabolism of drugs and other xenobiotics. It is defined by the U.S. National Library of Medicines IUPAC Glossary of Terms Used in Toxicology as the Supernatant fraction obtained from an organ (usually liver) homogenate by centrifuging at 9000 g for 20 minutes in a suitable medium; this fraction contains cytosol and microsomes. The microsomes component of the S9 fraction contain cytochrome P450 isoforms (phase I metabolism) and other enzyme activities. The cytosolic portion contains the major part of the activities of transferases (phase II metabolism). The S9 fraction is easier to prepare than purified microsomes. ...
Page 388 378 ENZYME SYSTEMS THAT METABOLISE Farmacocinetia AND OTHER XENOBIOTICS 1995; Dufort et al. Background correction is propranolol farmacocinetica farmacodinamia since about 30 of the activity in the left ventricle is contributed by noncardiac structures.
When a foreign compound enters the bloodstream, the body attempts to remove it using different metabolic processes. All compounds that enter the bloodstream from the gastrointestinal tract first pass through the liver, the site of most xenobiotic metabolism. The liver expresses a wide variety of enzymes that chemically alter blood-borne toxins and chemicals. Active transport or carrier proteins import xenobiotics or drugs into and export metabolites out of liver cells. Enzymes involved in phase I metabolism (cytochrome P450 enzymes) first modify these chemicals with polar functional groups using reactions such as oxidation, reduction, and hydrolysis. Enzymes involved in phase II metabolism (transferases and hydrolases) next conjugate these newly polar metabolites and electrophilic xenobiotics with inactive groups such as glutathione, glucuronic acid, amino acids, or sulfonates. Ultimately, this process generates larger and more polar metabolites than the original xenobiotic, making them easier ...
Expression of human cytochrome P450 (CYP) genes in human adult and fetal liver were studied using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. In adult liver mRNA of CYPs 1A1, 1A2, 2A6/2A7, 2B6/2B7, 2C8-19, 2D6, 2E1, 3A3/3A4 and 3A7 were detected while CYPs 2F1 and 4B1 were a …
Highlights advances in the understanding of the biosynthesis of xenobiotic conjugates in mammals, fish, insects, and plants. Describes current methods for the isolation and identification of xenobiotic conjugates. Provides evidence for and implications of newly discovered novel xenobiotic conjugates and the biological significance and consequences of xenobiotic conjugates.
Sigma-Aldrich offers abstracts and full-text articles by [Katsuhide Igarashi, Satoshi Kitajima, Ken-ichi Aisaki, Kentaro Tanemura, Yuhji Taquahashi, Noriko Moriyama, Eriko Ikeno, Nae Matsuda, Yumiko Saga, Bruce Blumberg, Jun Kanno].
ISSX has an international base of members from more than 45 countries. Members are comprised fairly evenly between academic and industry groups and consist primarily of research scientists and future scientists in toxicology, pharmacology, molecular biology, and other disciplines related to the study of xenobiotics. ...
ISSX has an international base of members from more than 45 countries. Members are comprised fairly evenly between academic and industry groups and consist primarily of research scientists and future scientists in toxicology, pharmacology, molecular biology, and other disciplines related to the study of xenobiotics. ...
Photochemical degradation of hydrophilic xenobiotics in the UV/H2O2-process. Influence of humic matter on the degradation rate of 2-amino-1-naphthalenesulfonate and ...
Spike-in SILAC, in which tissue from a single metabolically labeled mouse can be used as an internal standard in multiple experiments (39), permits large-scale analysis of the proteome without the expensive requirement for maintenance of a labeled mouse colony. Relative quantification of proteins of interest can only be achieved, however, when those proteins are expressed at a detectable level in this animal. We have sought here to create a generic in vivo SILAC material suitable for quantification of as many DME, both basally expressed and requiring induction, as possible. Following simultaneous activation of Pxr, Car, and Ahr, we observed the widespread up-regulation of multiple Cyp, with an increase from 56 unique Cyp-derived peptides in untreated mice to 115 unique peptides following mixture-dosing (Fig. 3A). Crucially, the greatest induction was seen in the xenobiotic-metabolizing Cyps of the 1a, 2b, 2c, and 3a subfamilies (Fig. 3A), as opposed to those superfamily members with minor ...
How to Maximize the Use of DMPK and Drug-Drug Interaction Data Available in the Literature and Regulatory Reviews during Clinical Development of New Chemical ...
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Naturally occurring sources refers to psychoactive chemicals or their precursors that already exist in nature. This is in contrast to synthetic psychoactives which are artificially produced or designed in laboratories. These natural chemicals can often be reproduced synthetically as well, though notably they appear in nature or through human cultivation.
Cleaning brazed or soldered joints with Fuze-Clean Metal Preparation Chemicals can help your production stay free of contaminates throughout production.
During recent years there have been several incidents where symptoms of disease have been linked to consumption of food contaminated by chemical substances (e.g. TCDD). Furthermore, outbreaks of infections in food producing animals have attracted major attention with regards to the safety for consumers (e.g., BSE and influenza in chicken). As shown for several xenobiotics in an increasing number of experimental studies, even low-dose xenobiotic exposure may impair immune function over time, as well as microorganism virulence, resulting in more severe infectious diseases and possibly other diseases as well. Also, during ongoing infection, xenobiotic uptake and distribution is often changed resulting in increased toxic insult to the host. The interactions between infectious agents, nutrients, and xenobiotics have thus become a developing concern and new avenue of research in food toxicology, as well as in food-born diseases. From a health perspective, in the risk assessment of xenobiotics in our ...
The multixenobiotic/multidrug resistance (MXR/MDR) system controls transport of foreign molecules across the plasma membrane as a preventive measure before toxicity becomes apparent. The system consists of an efflux pump, ABCB1, and/or a member of the ABCC family. Ionic liquids are broadly used solvents with several unique properties such as wide liquid range, negligible vapor pressure, good thermal and chemical stability and extraordinary dissolution properties for organic and inorganic compounds. Ionic liquids containing imidazolium ring are frequently used as solvents in drug synthesis. Constitutive and induced amounts of ABCB1 and ABCC1 proteins were estimated here by Western blotting and quantified by flow cytometry in HeLa cells exposed to three homologous 1-alkyl-3-methylimidazolium and one benzyl ring substituted salts. Aliphatic substituents in position 1 of the salts caused a weak toxicity but 1-benzyl ring was strongly toxic. An 8-day long treatment with 10-4 M ...
Their functions and localisation can expose gill cells to volume changes. To maintain their vital functions, these gill cells must regulate their own volume after cellular swelling or shrinkage. Recently, we showed that rainbow trout pavement gill cells in primary culture have the capacity to regula …
Transcriptional regulation of some genes involved in xenobiotic detoxification and apoptosis is performed via the human pregnane X receptor (PXR) which in turn is activated by structurally diverse agonists including steroid hormones. Activation of PX
Nuclear receptor humanized mice models have been developed to predict regulation of drug metabolizing enzyme by xenobiotics. However, limited information is available concerning xenobiotic-induced regulation of drug metabolizing enzymes in multiple nuclear receptor humanized mice. The present study investigated the hepatic regulation of cytochrome P450s (CYPs) and UDP-glucuronosyl-transferases (UGTs) in the pregnane X receptor (PXR) and the constitutive androstane receptor double humanized mice treated with rifampicin (RIF; 10 mg/kg) for 4 days. RIF increased hepatic microsomal protein and total CYP contents, and CYP reductase activity in the humanized mice, but not in normal mice. Moreover, hepatic induction of Cyp2b10, Cyp2c, and Cyp3a11 were observed only in the RIF-treated humanized mice, suggesting that the humanized mice are sensitive to RIF with respect to the regulation of the hepatic CYP system. Hepatic UGT activities using estradiol, serotonin, and mefenamic acid, but not ...
This study provides new insights into the mechanisms underlying the carcinogenic effects of tobacco smoke. Multiple genes encoding enzymes (CYP1A1, CYP1B1, AKRs, ALDH3A1, NQO1, and UGTs) involved in carcinogen metabolism were overexpressed in the oral mucosa of smokers. PAHs, an important class of tobacco carcinogen, are likely to mediate some of these expression changes. The AHR, a ligand-activated transcription factor, binds with high affinity to PAHs. Following ligand binding, the AHR translocates to the nucleus where it forms a heterodimer with ARNT. The AHR-ARNT heterodimer then binds to xenobiotic-responsive elements in the upstream regulatory region of target genes, resulting in the transcriptional activation of a network of genes, including CYP1A1 and CYP1B1 (33). The activation of AHR-mediated signaling leading to induction of xenobiotic metabolism provides a first line of defense against environmental carcinogens. However, the induction of xenobiotic-metabolizing enzymes by ...
The Journal of Xenobiotics publishes original studies concerning the beneficial (pharmacology) and detrimental effects (toxicology) of xenobiotics in all organisms. A xenobiotic (stranger to life) is defined as a chemical that is not usually found at significant concentrations or expected to reside for long periods in organisms. In addition to man-made chemicals, natural products could also be of interest if they have potent biological properties, special medicinal properties or that a given organism is at risk of exposure in the environment. Topics dealing with abiotic- and biotic-based transformations in various media (xenobiochemistry) and environmental toxicology are also of interest.. Areas of interests include the identification of key physical and chemical properties of molecules that predict biological effects and persistence in the environment; the molecular mode of action of xenobiotics; biochemical and physiological interactions leading to change in organism health; ...
Although the hPXR-LBD is similar to known nuclear receptor LBDs, it contains several distinct features that appear critical to its function as a promiscuous xenobiotic receptor. First, the variable region between α1 and α3 is a four-residue turn in the hPXR-LBD (Fig. 1A). In the PPARs, this region contains α2 and is the proposed ligand access site for the binding pocket (21, 26). Second, α6 is replaced in the hPXR-LBD by a conserved, flexible loop (residues 309 to 321) that lies adjacent in space to the ligand-binding cavity and may be involved in accommodation of both small and large ligands in the binding pocket. Third, the hPXR-LBD has two additional β strands not observed previously in a nuclear receptor LBD (Fig. 1A) (17). These form the fourth (β1, residues 210 to 217) and fifth (β1′, residues 221 to 226) strands of a five-stranded antiparallel β sheet (Fig. 1B). An insertion domain containing roughly the same number of residues (but only 12% sequence identity) was engineered ...
Studies were carried out on the developmental profile of PB-cytochrome P-450 and cytochrome P-448-dependent mixed-function oxidase activities in the foetal and neonatal rat. PB-Cytochrome P-450 activity, as examplified by benzphetamine N-demethylase was low at birth but increased with age. In contrast, cytochrome P-448 activity, as exemplified by ethoxyresorufin 0-deethylase (EROD) and biphenyl 2-hydroxylase, was higher in the neonate, reaching maximum levels at about two weeks postpartum and decreased with age. Cytochrome P-448 inducibility by 3-methylcholanthrene was low at birth and increased with age. Investigations were also carried out on the induction of cytochrome P-448, as measured by the 0-deethylation of ethoxyresorufin, by carcinogens and several other xenobiotics in hepatic and extrahepatic tissues of the adult male rat. EROD activity was highest in the liver, followed by the kidney , lung, in the untreated animal; activity was not detectable in the heart and the brain. Treatment ...
Püttmann, M., Arand, M., Oesch, F., Mannschreck, Albrecht and Robertson, L. (1990) Chirality and the Induction of Xenobiotic-Metabolizing Enzymes: Effects of the Atropisomers of 2,2;3,4,4;6-Hexachlorobiphenyl. In: Holmstedt, Bo and Frank, H. and Testa, B., (eds.) Chirality and biological activity: proceedings of an international symposium, Tübingen, Federal Republic of Germany, April 5 - 8, 1988. Liss, New York, p. 177. ISBN 0-471-56226-2. Fulltext not available ...
Enzymatic conversion of most xenobiotic compounds is accomplished by hepatocytes in the liver, which are also an important target for the manifestation of the toxic effects of foreign compounds. Most cell lines derived from hepatocytes lack important toxifying or detoxifying enzymes or are defective in signaling pathways which regulate expression and activity of these enzymes. On the other hand, the use of primary human hepatocytes is complicated by scarce availability of cells and high inter-donor variability. Thus, analyses of drug metabolism and hepatotoxicity in vitro are a difficult task. The cell line HC-AFW1 was isolated from a pediatric hepatocellular carcinoma and so far has been used for tumorigenicity and chemotherapy resistance studies. Here, a comprehensive characterization of xenobiotic metabolism in HC-AFW1 cells is presented along with studies on the functionality of the most important transcriptional regulators of drug-metabolizing enzymes. Results from HC-AFW1 cells were ...
Overexpression of BCRP/ABCG2, a xenobiotic efflux transporter, is related to anticancer drug resistance in tumors. Proto-oncogene c-MET induces cancer cell proliferation, motility, and survival, and its aberrant activation was found to be a prognostic factor in advanced ovarian cancers. In this study, we demonstrate the potential cross-resistance of doxorubicin-resistant ovarian cancer cells to the pheophorbide a (Pba)-based photodynamic therapy (PDT) and suggest c-MET and BCRP/ABCG2 overexpression as an underlying molecular mechanism. The doxorubicin resistant A2780 cell line (A2780DR) showed enhanced resistance to PDT cytotoxicity with decreased level of reactive oxygen species generation and Pba accumulation than A2780. In microarray analysis, BCRP/ABCG2 is the sole drug transporter which was upregulated in A2780DR. The incubation with the BCRP/ABCG2 specific inhibitor reversed the both Pba-PDT and doxorubicin resistance in A2780DR. Importantly, we identified that the expression of c-Met, ...
Almost without exception, biological processes such as overt morphological changes, development (both reproductive and growth), toxicological responses and clinical manifestation to disease, have molecular basis. From our perspective (i.e. toxicological perspective), the evidence of receptor-mediated mechanisms of xenobiotic-induced effects is provided if the effect is tissue specific, predictable, if increases in the transactivation of specific genes can be demonstrated, transcriptional responses occur rapidly, compounds bind reversibly to intracellular macromolecules or compounds are stereo-specific. Thus, the primary objective of toxicological in vitro studies on cells and tissues is to characterize cellular and molecular substrates and pathways that contribute to adverse effects in an organism after toxicant exposure. The estrogenic and xenobiotic biotransformation gene expressions are receptor-mediated processes that are ligand structure-dependent interactions with estrogen-receptor (ER) ...
While oxidative stress is a commonly cited toxicological mechanism, conventional methods to study it suffer from a number of shortcomings, including destruction of the sample, introduction of potential artifacts, and a lack of specificity for the reactive species involved. Thus, there is a current need in the field of toxicology for non-destructive, sensitive, and specific methods that can be used to observe and quantify intracellular redox perturbations, more commonly referred to as oxidative stress. Here, we present a method for the use of two genetically-encoded fluorogenic sensors, roGFP2 and HyPer, to be used in live-cell imaging studies to observe xenobiotic-induced oxidative responses ...
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Slide Set: Introduction to Chemical Mixtures. A biologist must be able to work with and understand a variety of mixtures. Dr. David Caprette presents basic concepts and definitions, and the rationale behind descriptions of types of mixtures. Companion slide set for the video, Introduction to Chemical Mixtures.
Urine is also being actively considered as a fertilizer for use in food-crop agriculture in developed countries. Studies into its feasibility and safety usually indicate that it is an acceptable alternative to chemical fertilisers and stabilised sludge. However, the technology to implement its use on a large scale has not been developed, and is considered too expensive. There are also concerns over its safety regarding the potential for transmitting infectious disease and refluxing xenobiotic compounds (associated with toilet-cleaning products and prescribed drugs expelled in urine) in the human food chain. Proponents of adopting urine for this use usually claim the risks to be negligible or acceptable, and point out that sewage causes more environmental problems when it is treated and disposed of compared with when it is used as a resource. Critics generally agree that more research is needed into how the resource is to be collected, processed and handled ...
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Cytochrome P450 3A4 (CYP3A4) plays a central role in xenobiotic metabolism, and is of critical importance to both human health and the pharmaceutical industry. Its ability to interact with multiple molecules of the same ...
The science of toxicology has progressed considerably since Molecular Toxicology was first published in 1997. New advances in biochemical and molecular biological experimental techniques have helped researchers understand the precise effects of toxins and foreign compounds on living things at the molecular, cellular, and organismal levels.
To our knowledge, the current study represents the largest and most comprehensive flow cytometric. Each case was assigned one of the following histological subtypes: ADCA, SCCA, Adeno-squamous,. The largest sample size of centenarians in GWAS studies published. Before the current study, starch, sucrose and xenobiotic metabolism and calcium signaling had not been identified as being.. What Does Threshold Mean In Science Dec 1, 2014. Learners do not just cross a conceptual threshold; they build it as they. chemical and physical behavior might mean very different things to. To maintain a high level of much-needed protection, we provided them with a private jet flight, he tweeted. To support. What does all of this blinking really mean. even. The treatment of bone defects remains one of the largest challenges in musculoskeletal TERM. and in situ differentiation in the absence of any growth factors, small molecular drugs, or genes. This.. 3b). The largest group of transcripts responding after 2 h ...
Xenoestrogens are chemicals that you are exposed to (and are hard to avoid in the modern world) that have an estrogenic effect in your body. Excess exposure to these can cause hormone balance disruptions for both men and women. So if you thought this article was just for the guys, these chemicals can wreak havoc in the body for both guys and gals ...
The Immunotoxicity of Workplace Xenobiotics interagency agreement functions to enhance the immunotoxicological evaluations of humans exposed to quantifiable lev...
The Mammalian Phenotype (MP) Ontology is a community effort to provide standard terms for annotating phenotypic data. You can use this browser to view terms, definitions, and term relationships in a hierarchical display. Links to summary annotated phenotype data at MGI are provided in Term Detail reports.