Urokinase plasminogen activator (uPA) system regulates extracellular matrix remodeling by activating ubiquitous protease plasmin. The system is involved in various physiological and pathological processes and its regulation is cell specific involving the regulation of proenzyme, its inhibitors and receptor. This thesis describes the regulation of uPA system in A1235 glioblastoma cells, deficient in alkylation damage repair, after the treatment with poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor and alkylating agent N-methyl-N-nitro-N-nitrosoguanidine (MNNG). MNNG has induced an increase in uPA activity in the narrow range of concentrations, under the conditions of high viability and the cell cycle arrest. In these experimental conditions, inhibition of PARP-1 has modulated induced uPA activity influencing the process of DNA repair. Increase in uPA activity was a consequence of change in the balance between uPA and its inhibitor PAI-1 expression and involved various signaling pathways. In the ...

Expression of the Escherichia coli aidB gene is induced in vivo by alkylation damage in an ada-dependent pathway and by anaerobiosis or by acetate at pH 6.5 in an ada-independent fashion. In this report, we present data on aidB gene structure, function, and regulation. The aidB gene encodes a protein of ca. 60 kDa that is homologous to several mammalian acyl coenzyme A dehydrogenases. Accordingly, crude extracts from an aidB-overexpressing strain showed isovaleryl coenzyme A dehydrogenase activity. aidB overexpression also reduced N-methyl-N-nitro-N-nitrosoguanidine-induced mutagenesis. Both ada- and acetate/pH-dependent induction of aidB are regulated at the transcriptional level, and the same transcriptional start point is used for both kinds of induction. Ada protein plays a direct role in aidB regulation: methylated Ada is able to bind to the aidB promoter region and to activate transcription from aidB in an in vitro transcription-translation system using crude E. coli extracts.

The MutS protein of Escherichia coli is part of the dam-directed MutHLS mismatch repair pathway which rectifies replication errors and which prevents recombination between related sequences. In order to more fully understand the role of MutS in these processes, dominant negative mutS mutations on a multicopy plasmid were isolated by screening transformed wild-type cells for a mutator phenotype, using a Lac+ papillation assay. Thirty-eight hydroxylamine- and 22 N-methyl-N-nitro-N-nitrosoguanidine-induced dominant mutations were isolated. Nine of these mutations altered the P-loop motif of the ATP-binding site, resulting in four amino acid substitutions. With one exception, the remaining sequenced mutations all caused substitution of amino acids conserved during evolution. The dominant mutations in the P-loop consensus caused severely reduced repair of heteroduplex DNA in vivo in a mutS mutant host strain. In a wild-type strain, the level of repair was decreased by the dominant mutations to between 12 to

Monoclonal antibody (MAb) 17E4 reacts with a surface carbohydrate determinant and agglutinates cells of Candida albicans. Using this MAb, we have isolated N-methyl-N-nitro-N-nitrosoguanidine-induced nonagglutinating mutants. Eleven of these were characterized for the presence and expression of the surface antigen recognized by MAb 17E4 by immunoblot analysis of whole cells and by fluorescence flow cytometry. Soluble cell wall extracts from five mutant strains were negative by immunoblot analysis. The reactivities of the strains with several other MAbs and commercial antisera (Candida Check; Iatron Laboratories, Tokyo, Japan) which also recognize carbohydrate determinants were examined by immunoblot analysis of whole cells. Mutant strains showed no or reduced expression of the MAb 17E4 antigen and could be placed into at least two distinct phenotypic classes. Recognition by the other MAbs tested showed a similar pattern, while recognition by the commercial antisera was unchanged in the mutant ...

The role of the lung in stomach carcinogenesis is discussed, and a revision of the Meyer hypothesis of stomach carcinogenesis is presented. According to the Meyer hypothesis, the risk for lung or stomach cancer in susceptible individuals is related to pulmonary clearance of carcinogenic particles as follows: the risk of lung cancer is decreased when particle retention in the lungs is increased and

The c1 (B6NLxv1c2) line was derived from Hepa-1c1c7 (ATCC CRL-2026). Hepa-1c1c7 has high CYP1A1-dependent aryl hydrocarbon hydroxylase (AHH) activity. N-methyl-N-nitro-N-nitrosoguanidine (MNNS) mutated colonies were selected for benzo[a]pyrene resistance. The c1 (B6NLxv1c2) cell line lacks cytochrome P4501A1 dependent aryl hydrocarbon hydroylase (AHH) activity due to a single point mutation in CYP1A1 leading to premature termination of the translated protein (Asn-414; 56 kDa to 45 kDa). The line may be used to study xenobiotic (and carcinogenic) metabolism in the absence of cytochrome P4501A1 activity, which is known to metabolize cytotoxic and carcinogenic intermediates. It is also a tool to study the putative natural ligand for the induction of this enzyme.

Two Chinese hamster ovary (CHO) cell variants differ substantially in their sensitivity to N-methyl-N -nitro-N-nitrosoguanidine (MNNG). The resistant clone (Cl 3) was isolated from the sensitive...

Clonal subpopulations of a chemically induced tumorigenic rat liver epithelial cell line were analyzed for their cellular, biochemical, and in vitro growth properties and their tumorigenicity after injection into day-old newborn isogeneic rats. The phenotypic properties studied included DNA content; growth rate in culture; activities of γ-glutamyl transpeptidase, NADH diaphorase, pyruvate kinase, glucose-6-phosphate dehydrogenase, and lactate dehydrogenase; ability to grow in calcium-poor medium; and ability to form colonies in soft agar. The results show that none of these phenotypes cosegregates with tumorigenicity and therefore is not reliable as a marker phenotype for neoplastic transformation in cultured rat liver epithelial cells. The poor correlations, either qualitatively or quantitatively, between paratumorigenic phenotypes and tumorigenicity suggest that neoplastic transformation in these cells involves a specific transforming gene locus or loci and that in vitro paratumorigenic ...

Asllani FH, Schürz M, Bresgen N, Eckl PM, Alija AJ. (2019) Genotoxicity risk assessment in fish (Rutilus rutilus) from two contaminated rivers in the Kosovo. In: Sci Total Environ. 676, 429-435. doi: 10.1016/j.scitotenv.2019.04.321. Khader M, Eckl PM, Bresgen N. Effects of aqueous extracts of medicinal plants on MNNG-treated rat hepatocytes in primary cultures. J Ethnopharmacol, 2007; 112(1):199-202 Bosch K, Erdinger L, Ingel F, Khussainova S, Utegenova E, Bresgen N, Eckl PM. Evaluation of the toxicological properties of ground- and surface-water samples from the Aral Sea Basin. Sci Total Environ, 2007; 374(1):43-50. Schöllnberger, H. and Eckl, P.M. (2007) Protective bystander effects simulated with the state-vector model. Dose Response 5, 187-203. Bresgen N, Fiedler B, Ohlenschläger I, Wacht N, Zach S, Dunkelmann B, Hochleitner E, Lottspeich F, Eckl PM. Ferritin-a mediator of apoptosis? J Cell Physiol, 2007; 212(1):157-64. Ohlenschläger, I., Bresgen, N. and Eckl, P.M. (2007) A novel ...

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Fingerprint Dive into the research topics of Chemically induced mutations in mitochondrial dna of human cells: Mutational spectrum of N-methyl-N-nitro-N-nitrosoguanidine. Together they form a unique fingerprint. ...

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The statistical analysis (one way ANOVA and Tukey-Kramer multiple comparison test) further proved that the differences between wild type and mutants were significant (Table 2). For biomass, the wild type, YlB2 and YlC7 belonged to the same group while YlB6 and YlE1 belonged to separate groups. The lipid yields of all mutants and the wild type differed and were separately grouped. For YL/X, notably, YlB6, YlC7 and YlE1 showed significantly higher values and were separately grouped. For QX, the wild type, YlC7 and YlB2 belonged to the same group. For QL, the wild type, YlB6, YlC7 and YlE1 belonged to different groups and were again significantly higher as compared to the wild type.. On the basis of the results obtained from the MNNG treatment, YlB6 was selected because its cultures showed the maximum biomass, total lipid yield and volumetric biomass and lipid productivities. The mutant YlC7 was also selected because it showed a lipid content of 60% and an increased lipid productivity as compared ...

Step (a) of the above method of the invention is preferably performed using doped primers. For instance, the random mutagenesis may be performed by use of a suitable physical or chemical mutagenizing agent, by use of a suitable oligonucleotide, or by subjecting the DNA sequence to PCR generated mutagenesis. Furthermore, the random mutagenesis may be performed by use of any combination of these mutagenizing agents. The mutagenizing agent may, e.g., be one, which induces transitions, transversions, inversions, scrambling, deletions, and/or insertions. Examples of a physical or chemical mutagenizing agent suitable for the present purpose include ultraviolet (UV) irradiation, hydroxylamine, N-methyl-N-nitro-N-nitrosoguanidine (MNNG), O-methyl hydroxylamine, nitrous acid, ethyl methane sulphonate (EMS), sodium bisulphite, formic acid, and nucleotide analogues. When such agents are used, the mutagenesis is typically performed by incubating the DNA sequence encoding the parent enzyme to be mutagenized ...

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A number of possible preventive agents for cancers in different organs have been reported, however, little information is available regarding the effective agents for the development of gastric cancers. The rice components are known to be effective for the prevention of the development of cancers. Our group has demonstrated that fermented brown rice by Aspergillus Orzae (FBRA) has chemopreventive potentials in several organs. In this study, we investigated the modifying effects of FBRA exposed during the initiation or post-initiation phase of N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in rats. Five-week-old male ACI rats were divided into 7 groups. Groups 1-5 were given oral administration of MNNG (100 mg/l in distilled water) for 24 weeks starting at 6 weeks of age. Groups 2 and 3 were fed a diet containing 5 and 10% FBRA during the initiation phase, respectively, whereas groups 4 and 5 were fed these diets during the post-initiation phase. Group 6 was given a ...

Mouse monoclonal Poly (ADP-Ribose) Polymer antibody [10H]. Validated in IHC and tested in Rat, Human. Cited in 31 publication(s). Independently reviewed in 12 review(s). Immunogen corresponding to -.

Covers the history of clinical and experimental gastric cancer research Updated issues of molecular and pathological research on gastric carcinogenesis

This usually occurs as a focal or multifocal event and may be seen as an aging change in rats. Glandular dilation usually involves multiple glands, and the dilatation is often irregular in profile (i.e., not a well-circumscribed circular structure). Glandular cysts (see Stomach, Glandular stomach, Glands - Cyst) are usually solitary, larger, and lined by attenuated epithelium ...

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Following treatment with the mutagen N-methyl-N-nitro-N-nitrosoguanidine, three mutants of Lactococcus lactis subsp. lactis biovar diacetylactis CNRZ 483 that produced diacetyl and acetoin from glucose were isolated. The lactate dehydrogenase activity of these mutants was strongly attenuated, and the mutants produced less lactate than the parental strain. The kinetic properties of lactate dehydrogenase of strain CNRZ 483 and the mutants revealed differences in the affinity of the enzyme for pyruvate, NADH, and fructose-1,6-diphosphate. When cultured aerobically, strain CNRZ 483 transformed 2.3% of glucose to acetoin and produced no diacetyl or 2,3-butanediol. Under the same conditions, mutants 483L1, 483L2, and 483L3 transformed 42.0, 78.9, and 75.8%, respectively, of glucose to C4 compounds (diacetyl, acetoin, and 2,3-butanediol). Anaerobically, strain CNRZ 483 produced no C4 compounds, while mutants 483L1, 483L2, and 483L3 transformed 2.0, 37.0, and 25.8% of glucose to acetoin and 2,3-butanediol. In

In this study, we determined the role of COX-2 inhibition in the prevention of sodium chloride enhanced gastric carcinogenesis induced by MNNG in Wistar rats. MNNG induced gastric cancer is a well established animal model of stomach carcinogenesis.16 The mutagen, when given in drinking water, induces intestinal metaplasia and adenocarcinoma in the pyloric mucosa of Wistar rats.1620 The histology of this induced gastric malignancy resembles the differentiated type of stomach cancer in humans. To enhance the carcinogenic effects of MNNG, highly concentrated sodium chloride solution was given to these animals in the initial six weeks.17 In the present study, 75% of MNNG treated animals developed gastric cancer at the end of 48 weeks, confirming that this is a highly successful model of gastric tumorigenesis.. Although the exact mechanism underlying MNNG induced gastric cancer remains poorly understood, previous studies showed that the genetic makeup of the animals may play a role.21 For example, ...

e deficient for the mismatch repair (MMR) gene Msh2 show accelerated tumourigenesis and a reduced apoptotic response to DNA damage of methylation type. Here we examine the effect of mutation for Msh2 on in vivo mutation frequencies in the intestine as determined by loss of function at the Dolichos biflorus (Dlb-1) locus. Spontaneous mutation frequencies were scored in cohorts of ageing mice either wild type or mutant for Msh2. In mice less than 1 year old, mutation frequencies were only elevated in Msh2 null mice. However, beyond this age heterozygous Msh2 mice showed significantly higher mutation frequencies than controls. These findings implicate a gene dose dependent requirement for Msh2 in mutation suppression and prompted an analysis of young Msh2 mutants following exposure to DNA damage. Following exposure to N-methyl-N-nitro-N-nitrosoguanidine (MNNG), Msh2 deficient mice show a reduced apoptotic response and an increase in mutation frequency. Heterozygotes did not differ from controls. ...

Expression of ECM proteins fibulin-1 and -2 in acute and chronic liver disease and in cultured rat liver cells. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.

www.MOLUNA.de Chemical Mutagens [4200674] - The best protection against environmental mutagens is to identify them before they ever come into general use. But it is always possible that some substance will escape detection and affect a large number of persons without this being realized until later generations. This article considers ways in which such a

If you use this products in your scientific publication, it should be cited in the publication as: Creative Bioarray cat no. If your paper has been published, please click here to submit the Pub Med ID of your paper to get a coupon. ...

Melphalan is a DNA alkylating agent; induces cytotoxicity through the formation of stable interstrand and intrastrand crosslinks within DNA which inhibits growth of PC-3 cells (IC50 values are 0.074 and 0.77 μM for sequential dosing and single dosing respectively). Learn More ...

We examined whether superoxide is a factor responsible for paraquat-induced liver injury in terms of superoxide dismutase using cultured rat liver slices exposed to various concentrations of paraquat. The degree of liver injury was assessed by measurement of percentage of lactate dehydrogenase leakage into the medium and lipid hydroperoxides in the liver slices and by direct histopathological observation. Paraquat produced concentration- and time-related liver injury in the cultured rat liver slices. Notably, after exposure to 5 mmol/L paraquat, a significant increase of the percentage of lactate dehydrogenase leakage occurred from 4 hr (p , 0.05 vs. control group), and this gradually increased up to 8 hr (p , 0.01 and p , 0.001 vs. control group at 6 and 8 hr, respectively). Changes in lipid hydroperoxides in the liver slices were similar to those in percentage of lactate dehydrogenase leakage (p , 0.05 and p , 0.01 vs. control group at 6 and 8 hr, respectively). Liver injury was located around ...

We have used site-directed mutagenesis to alter bases in lacZ near the region encoding essential residues in the active site of beta-galactosidase. The altered sequences generate runs of six or seven identical base pairs which create a frameshift, resulting in a Lac- phenotype. Reversion to Lac+ in each strain can occur only by a specific frameshift at these sequences. Monotonous runs of As (or of Ts on the opposite strand) and Gs (or Cs) have been constructed, as has an alternating -C-G- sequence. These specific frameshift indicator strains complement a set of six previously described strains which detect each of the base substitutions. We have examined a variety of mutagens and mutators for their ability to cause reversion to Lac+. Surprisingly, frameshifts are well stimulated at many of these runs by ethyl methanesulfonate, N-methyl-N-nitro-N-nitrosoguanidine and 2-amino-purine, mutagens not widely known to induce frameshifts. A comparison of ethyl methanesulfonate, ...

Connexin32 inhibits gastric carcinogenesis through cell cycle arrest and altered expression of p21Cip1 and p27Kip1;kpubs;kpubs.org

Poly(ADP-ribose) polymerase 1 (PARP-1) and poly(ADP-ribose) glycohydrolase (PARG) regulate transcriptional activity by modifying target nuclear proteins with the addition and removal of ADP-ribose polymers, respectively. While the role of PARP-1 has been established, the exact function of PARG in the nucleus is less clear, although its assumed that PARP-1 and PARG have opposing functions in gene regulation. In this article, however, the authors show that this is not the case. Combining short hairpin RNA (shRNA) knockdown with microarray analysis in MCF-7 cells, they determined that these two enzymes often act in a similar, rather than antagonistic, manner. PARP-1 and PARG generally localized to similar target promoters, most notably in genes for stress response and metabolism, and, in about half of the genes tested, PARP-1 binding was dependent on PARG. In addition, studies using shRNA-resistant catalytic mutants revealed that enzymatic activity was not required in some target genes. So, rather ...

TY - JOUR. T1 - Inactivation and degradation of O6-alkylguanine-DNA alkyltransferase after reaction with nitric oxide. AU - Liu, Liping. AU - Xu-Welliver, Meng. AU - Kanugula, Sreenivas. AU - Pegg, Anthony E.. PY - 2002/6/1. Y1 - 2002/6/1. N2 - O6-Alkylguanine-DNA alkyltransferase (AGT) plays a critical role in protection from the carcinogenic effects of simple alkylating agents by repairing O6-alkylguanine adducts via a direct transfer reaction. Nitric oxide (NO) or species derived from it are known to be able to initiate neoplastic growth and cannot only damage DNA, either directly or via the formation of intermediates such as nitrosamines, but can also inhibit some DNA repair processes. We have studied the inactivation of AGT by NO in detail in vitro and in vivo using wild-type human AGT (hAGT) and mutants at key residues. Our results show that hAGT is readily but reversibly inactivated by the formation of S-nitrosylcysteine at Cys-145, which is the alkyl acceptor site. The facile reaction of ...

O6-methylguanine-DNA methyltransferase plays vital roles in preventing induction of mutations and cancer as well as cell death related to alkylating agents. Mice defective in the Mgmt gene, encoding the methyltransferase, were used to evaluate cell death-inducing and tumorigenic activities of therapeutic agents which have alkylation potential. Mgmt-/- mice were considerably more sensitive to dacarbazine, a monofunctional triazene, than were wild-type mice, in terms of survival. When dacarbazine was administered i.p. to 6-week-old mice and survival at 30 days was enumerated, LD50 values of Mgmt-/- and Mgmt+/+ mice were 20 and 450 mg/kg body wt, respectively. Increased sensitivity of Mgmt-/- mice to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), a bifunctional nitrosourea, was also noted. On the other hand, there was no difference in survival of Mgmt+/+ and Mgmt-/- mice exposed to cyclophosphamide, a bifunctional nitrogen mustard. It appears that dacarbazine and ...

https://doi.org/10.18632/oncotarget.10440 Jennifer A. Calvo, Mariacarmela Allocca, Kimberly R. Fake, Sureshkumar Muthupalani, Joshua J. Corrigan, Roderick T. Bronson, Leona D. Samson

https://doi.org/10.18632/oncotarget.10440 Jennifer A. Calvo, Mariacarmela Allocca, Kimberly R. Fake, Sureshkumar Muthupalani, Joshua J. Corrigan, Roderick T. Bronson, Leona D. Samson

Alkylating drug definition, any of various potentially cytotoxic, carcinogenic, and mutagenic substances: used therapeutically to destroy cells, especially proliferating cancer cells. See more.

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Interleukin-1 beta (IL-1 beta) is one of the proinflammatory cytokines that may mediate primary nonfunction of islets of Langerhans, limiting the success of allogeneic transplantation. The aim of this study was to assess differences between the secretion of IL-1 beta as well as glycemia in periand long-term periods of intraportal islet allo-transplantation with or without cyclosporine (CyA) immunosuppression. Inbred Wistar albino rats were transplanted intraportally with rat islets isolated by collagenase digestion. The two recipient groups (6 rats/group) were: group 1, control, islet transplantation (ITX) without any treatment and group 2, CyA-treated via the femoral muscle on days -1, 0, +1, and +2. Serum IL-1 beta (pg/mL) levels were measured by ELISA on days 0 (pre-ITX), +1, +2, and + 195. Tail vein blood was used to evaluate glycemia (mg/dL). No major differences were observed in IL-1 beta secretion on days 0, +1, or +195 between the groups. Immunosuppressive treatment produced ...

This retrospective study investigates the prognostic value of the EGF receptor, its phosphorylated form pEGFR Y1068, ß-catenin and MIB1 as well as the presence of CD3-positive lymphocytes in primarily resected stomach carcinoma by immunohistochemical staining of Tissue Micro Arrays. The analysis was performed using a light microscope and computer-based image analysis. As a result, the presence of CD3-positive lymphocytes and the expression of MIB1 had the strongest prognostic value ...

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Title:A Short Review on the Synthetic Strategies of Duocarmycin Analogs that are Powerful DNA Alkylating Agents. VOLUME: 15 ISSUE: 5. Author(s):Pravin C. Patil, Vijay Satam and Moses Lee. Affiliation:Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA.. Keywords:Antitumor-antibiotics, apoptosis, centanamycin, duocarmycins, tafuramycin A.. Abstract:The duocarmycins and CC-1065 are members of a class of DNA minor groove, AT-sequence selective, and adenine-N3 alkylating agents, isolated from Streptomyces sp. that exhibit extremely potent cytotoxicity against the growth of cancer cells grown in culture. Initial synthesis and structural modification of the cyclopropa[c] pyrrolo[3,2-e]indole (CPI) DNA-alkylating motif as well as the indole non-covalent binding region in the 1980s have led to several compounds that entered clinical trials as potential anticancer drugs. However, due to significant systemic toxicity none of the analogs have passed clinical evaluation. As a result, ...

1. Baylin SB, Ohm JE. Epigenetic gene silencing in cancer - a mechanism for early oncogenic pathway addiction?. Nat Rev Cancer. 2006;6:107-116 2. Laird PW. Principles and challenges of genome-wide DNA methylation analysis. Nat Rev Genet. 2010;11:191-203 3. Bhutani N, Brady JJ, Damian M. et al. Reprogramming towards pluripotency requires AID-dependent DNA demethylation. Nature. 2010;463:1042- 1047 4. Daura-Oller E, Cabre M, Montero MA. et al. Specific gene hypomethylation and cancer: New insights into coding region feature trends. Bioinformation. 2009;3:340-343 5. Tomita H, Hirata A, Yamada Y. et al. Suppressive effect of global DNA hypomethylation on gastric carcinogenesis. Carcinogenesis. 2010;31:1627-1633 6. Wang Z, Xu J, Geng X. et al. Analysis of DNA methylation status of the promoter of human telomerase reverse transcriptase in gastric carcinogenesis. Arch Med Res. 2010;41:1-6 7. McCabe MT, Brandes JC, Vertino PM. Cancer DNA methylation: molecular mechanisms and clinical implications. Clin ...

Modulation of DNA synthesis by 2,3,7,8-tetrachlorodi-benzo-p-dioxin (TCDD) was studied in primary cultures of hepatocytes and in rat liver epithelial cells (WB-F344) to develop models for studies on the interactions between the activated Ah receptor and cellular growth control. In hepatocytes TCDD either positively or negatively modulated EGF-stimulated DNA synthesis. In the presence of ethlnylestradiol 10−12 M TCDD moderately increased EGF-stimulated DNA synthyesis (∼30%). In contrast, 10−9 M TCDD in the absence of ethlnylestradiol decreased DNA synthesis (∼30%). Analysis of variance revealed that the TCDD effects were highly significant. The response of early genes of the jun/fos family and the corresponding proteins was also studied under these two conditions. In agreement with the DNA synthesis data, the level of c-Jun was increased or decreased in nuclear extracts. Further-more, DNA binding of Jun/Fos proteins, including c-Jun and Fra-1, was decreased under conditions of ...

ATCC ® Normal Human Primary Bronchial/Tracheal Epithelial Cells, when grown in Airway Epithelial Cell Basal Media supplemented with Bronchial/Tracheal Epithelial Cell Growth Kit components, provide an ideal cell system to propagate bronchial/tracheal epithelial cells in serum-free conditions. The cells are cryopreserved at the second passage to ensure the highest viability and plating efficiency. ATCC ® Primary Cell Solutions™ cells, media, supplements and reagents are quality tested together to guarantee optimum performance and reliability.

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Vegivinti, C. T. R., Pederson, J. M., Saravu, K., Gupta, N., Evanson, K. W., Kamrowski, S., Schmidt, M., Barrett, A., Trent, H., Dibas, M., Reierson, N. L., Mikoff, N., Pisipati, S., Joseph, B. A., Selvan, P. T., Dmytriw, A. A., Pulakurthi, Y. S., Keesari, P. R., Sriram, V., Chittajallu, S. & 8 others, Brinjikji, W., Katamreddy, R. R., Chibbar, R., Davis, A. R., Malpe, M., Mishra, H. K., Kallmes, K. M. & Hassan, A. E., 2021, (Accepted/In press) In: Journal of Clinical Apheresis.. Research output: Contribution to journal › Review article › peer-review ...

Guanazole and aphidicolin were chosen as candidates in the search for a selective, non-genotoxic inhibitor of DNA replication which could be used instead of hydroxyurea to measure DNA repair synthesis in rat hepatocyte primary cultures by liquid scintillation counting. The genotoxicity of these 3 chemicals was studied using the Salmonella/liver homogenate assay and the autoradiographic UDS test in hepatocytes. Hydroxyurea was positive in both of these assays. Guanazole and aphidicolin did not induce DNA repair in hepatocytes. Aphidicolin was not mutagenic for Salmonella typhimurium, whereas guanazole increased the revertant numbers of strain TA102 slightly. The incorporation of [3H]thymidine was measured by liquid scintillation to determine DNA repair induced by 2-acetylaminofluorene (2-AAF), aflatoxin B1, benzo[a]pyrene, cyclophosphamide, H2O2, 6-hydroxydopamine, N-methyl-N-nitro-N-nitrosoguanidine (MNNG), methylnitrosourea (MNU), 4-nitroquinoline-N-oxide and UV irradiation in the presence of ...

Alterations in protein synthesis in primary cultured rat liver parenchymal cells were examined after their exposure to the potent carcinogens, polychlorinated biphenyl (PCB) congeners. Co-planar PCB congeners (3,4,5,3′,4′-PCB and 3,4,5,3′,4′,5′-PCB) (10 nM) induced a protein, the Mr of which was 25,000 (25 k protein) under denaturing conditions. However, non-co-planar PCB congeners and several xenobiotics, which induce microsomal proteins, did not induce the 25 k protein. By using immunoblotting, the 25 k protein was identified as glutathione S-transferase P-form (GST-P, 7-7, EC 2.5.1.18).. ...

The tyrosine residue present at position 158 in the human O6-alkylguanine-DNA alkyltransferase is one of 22 amino acid residues that are conserved in all known alkyltransferase protein sequences. The importance of this amino acid in the reactions brought about by the alkyltransferase was studied by changing this residue to alanine or to phenylalanine. The control and mutant alkyltransferase proteins were expressed in an Escherichia coli strain lacking alkyltransferase activity and the proteins purified to near homogeneity and their activities measured using both methylated DNA and O6-benzylguanine (BG) as substrates. The alteration to alanine led to a very large decrease in activity towards both substrates but removal of O6-methylguanine from DNA and the conversion of BG to guanine could still be detected when large amounts of the protein were used. The activity of the Y158A mutant was at least 800 times less than that of the control alkyltransferase. The change of tyrosine-158 to phenylalanine reduced

Here, we demonstrate that OTUD4 may serve as a master regulator of alkylation damage resistance through stabilization of the human AlkB homologues. A number of distinct lines of evidence support this role for OTUD4. First, OTUD4 interacts specifically with ALKBH2 and ALKBH3 and encodes a K48‐specific DUB (Fig 1). Consistently, ALKBH3 is subjected to K48‐linked ubiquitination and proteasomal degradation (Fig 2A-D). OTUD4 antagonizes ALKBH3 ubiquitination and stabilizes both ALKBH2 and ALKBH3 in vivo (Fig 2E-H). ALKBH3 protein levels do not correlate well with ALKBH3 mRNA levels in various tumor cell lines but do correlate with OTUD4 levels (Supplementary Fig S2). Finally, overexpression of ALKBH3 in PC‐3 cells, which depend primarily on ALKBH3 instead of ALKBH2 for alkylation damage resistance, is sufficient to rescue alkylation damage sensitivity upon loss of OTUD4 (Fig 7G).. What is most striking is that we find OTUD4 catalytic activity to be apparently dispensable for its stabilization ...

We investigated sequence-specific DNA alkylation using conjugates between the N-methylpyrrole (Py)-N-methylimidazole (Im) polyamide and the DNA alkylating agent, chlorambucil, or 1-(chloromethyl)-5-hydroxy-1, 2-dihydro-3H-benz[e]indole (seco-CBI). Polyamide-chlorambucil conjugates 1-4 differed in the position at which the DNA alkylating chlorambucil moiety was bound to the Py-Im polyamide. High-resolution denaturing polyacrylamide gel electrophoresis (PAGE) revealed that chlorambucil conjugates 1-4 alkylated DNA at the sequences recognized by the Py-Im polyamide core moiety. Reactivity and sequence specificity were greatly affected by the conjugation position, which reflects the geometry of the alkylating agent in the DNA minor groove. Polyamide-seco-CBI conjugate 5 was synthesized to compare the efficacy of chlorambucil with that of seco-CBI as an alkylating moiety for Py-Im polyamides. Denaturing PAGE analysis revealed that DNA alkylation activity of polyamide-seco-CBI conjugate 5 was similar ...

Protein alkylation by reactive electrophiles contributes to chemical toxicities and oxidative stress, but the functional impact of alkylation damage across proteomes is poorly understood. We used Click chemistry and shotgun proteomics to profile the accumulation of proteome damage in human cells tre …

Weller, R. (2004): Post-depositional losses of methane sulfonate, nitrate, and chloride in Antarctic firn. , Blockseminar (Environmental Physics - University of Bremen & AWI Bremerhaven) 05 July 2004 Alfred-Wegener-Institut für Polar- und Meeresforschung Building F (glass hall seminar room), Bussestraße 24, Bremerhaven Topic: Interactions between Atmosphere, I ...

Burlington, VT - Today, Mayor Miro Weinberger released the following statement:. UVM has made huge efforts to keep its students, staff, and our community safe during the pandemic. Throughout, UVM also has been in close communication with the City, and has committed to step up its efforts even further if needed. Im appreciative that UVM is making good on that commitment today by moving from once-weekly to twice-weekly testing for all students, and also implementing other measures designed to identify positive cases and close contacts even sooner. I am grateful to the thousands of UVM and Champlain College students whose exceptional individual efforts and sacrifices are helping protect the Burlington community, and urge everyone to continue that work.. # # #. ...

Husted L, Jensen TK, Olsen SN, et. al. Examination of equine glandular stomach lesions for bacteria, including helicobacter spp by fluorescence in situ hybridisation. BMC Microbiol. 2010 Mar 19;10:84.Dryden V. Managing the Adult Club Foot. AAEP Proceedings, Focus on the Foot 2013:75-77. ...

Sorof, S and Dickens, M S., Evidence for similar principal target proteins of chemical carcinogens in six carcinogen-organ systems. Abstr. (1978). Subject Strain Bibliography 1978. 443 ...

Abstracted from an image by Simionescu and Simionescu in The Journal of Cell Biology (70:608-621), ©1976, The Rockefeller University Press. This imag...