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analysis
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development and evaluation of genotoxicity screening sensors measuring DNA damage from metabolsim of arylamines and based on ultrathin films containing DNA and N-acetyltransferase on pyrolytic graphite electrodes. N-acetyltransferase in the film catalyzes the conversion of the arylamine 2-aminofluorene to 2-acetylaminofluorene by acetyl coenzyme A-dependent N-acetylation. DNA damage is measured subsequently using ctaalytic voltammetric oxidation with Ru(bpy)32+
analysis
the NAT enzyme activates an arylhydroxamic acid functionality into a nitrenium ion that reacts fast, covalently, and under neutral conditions with nucleophilic residues of neighboring proteins. Strong labeling is only observed with an arylhydroxamic acid bearing an electron donating substituent. Clear labeling is achieved on a subcellular level in living cells that are transfected with a genetically targeted NAT to the nucleus or the cytosol
drug development
inhibitors of NAT enzymes may be valuable as chemopreventive agents
drug development
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the enzyme is a target for development of anti-mycobacterial drugs
drug development
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the enzyme is a target for development of anti-mycobacterial drugs
drug development
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the enzyme is a target for development of anti-mycobacterial drugs
drug development
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the enzyme is a target for development of anti-mycobacterial drugs
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medicine
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inactivation of antiopportunistic infection drugs
medicine
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activity in umbilical cord tissue from different samples
medicine
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activity in benign prostatic hyperplasia tissue
medicine
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kinetics of several substrates for different genetic variants of enzyme
medicine
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Nat2 expression may be useful as a marker in cardiac development
medicine
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the enzyme is a target for antituberculosis therapy
medicine
a polymorphic homologue of human NAT2 is characterized in the rhesus macaque, to facilitate investigations of the postulated involvement of this isoenzyme in the toxicogenetics of endometriosis
medicine
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altered expression of the human orthologue in breast tumours, in which there is endocrine signalling, suggests that human NAT1 should be considered as a potential biomarker for neuroendocrine tissues and tumours
medicine
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C1095A SNP outside the NAT1 coding region is associated with increased homocysteine. The C1095A SNP is found most frequently in the NAT1 allele 1*10 and is shown to have increase NAT1 activity or to have no effect. C1095A SNP appears at increased frequency in bladder cancer and Alzheimer's disease
medicine
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consensus gene nomenclature is necessary to report and interpret the results of human epidemiological studies, as well as to perform meta analysis and, or compare the results of different studies
medicine
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consensus gene nomenclature is necessary to report and interpret the results of human epidemiological studies, as well as to perform meta analysis and, or compare the results of different studies
medicine
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consensus gene nomenclature is necessary to report and interpret the results of human epidemiological studies, as well as to perform meta analysis and, or compare the results of different studies
medicine
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consensus gene nomenclature is necessary to report and interpret the results of human epidemiological studies, as well as to perform meta analysis and, or compare the results of different studies
medicine
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consensus gene nomenclature is necessary to report and interpret the results of human epidemiological studies, as well as to perform meta analysis and, or compare the results of different studies
medicine
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consensus gene nomenclature is necessary to report and interpret the results of human epidemiological studies, as well as to perform meta analysis and, or compare the results of different studies
medicine
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epidemiological studies of birth defects indicate that NAT1 polymorphisms are associated with problems of neural tube closure in spina bifida and with cleft lip and palate. Limp formation defects are also associated with NAT1 polymorphism
medicine
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genetic profile of the NAT2 gene in individuals from two different regions of Brazil: Rio de Janeiro and Goi´as States is examined in 404 individuals: 13 previously described SNPs are detected in these Brazilian populations, from which seven are the most frequent in other populations. Upon allele and genotype analysis, the most frequent NAT2 alleles are respectively NAT2*5B (33%), NAT2*6A (26%) and NAT2*4 (20%) being NAT2*5/*5 the more prevalent genotype (31.7%). Results demonstrate the predominance in the studied Brazilian groups of NAT2 alleles associated with slow over the fast and intermediate acetylator genotypes. Additionally, in Rio de Janeiro, a significantly higher frequency of intermediate acetylation status is found when compared to Goi´as (42.5% versus 25%),demonstrating that different regions of a country with a population characterized by a multi-ethnic ancestry may present a large degree of variability in NAT2 allelic frequencies
medicine
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HIV-infection in human decreases NAT2 activity but not NAT1
medicine
it is shown that human NAT1 is induced by androgens, which may have implications for cancer risk in individuals
medicine
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mutant alleles resulting in a decrease in NAT1 activity are found to be protective against spina bifida
medicine
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NAT is involved in drug induced liver injury. NAT metabolizes drugs causing liver damages: acetylsalicylic acid, dapsone, dihydralazine, isoniazid, p-aminosalicylic acid, procainomide, sulfasalazine, sulfanamide, mesalamine, maprotiline, flutamide
medicine
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NAT2 exerts the effects of drug combinations: NAT2 polymorphisms modify the doxycyline-rifampin interaction that occurs in individuals treated simulataneously with these drugs, that cause an inverse correlation between doxycycline rifampin plasma levels. Among individuals classified as rapid acetylators rifampin plasma levels are greater whereas doxycycline levels are lower, as compared to slow acetylators
medicine
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NAT2 polymorphisms in both promoter and coding regions in the Indonesian population are examined: Promoter and coding regions of NAT2 displays 23 polymorphisms/variations. Seven haplotypes in the promoter region and six haplotypes in the coding region are inferred. Haplotypes in promoter and coding regions show limited combinations, and 13 combined haplotypes are inferred. The most frequent haplotypes are U1 (38.9%), U2 (33.5%) in the promoter region and NAT2*4 (37.3%), NAT2*6A (36.8%) in the coding region. When converted to predicted phenotypes, the studied population comprise 65.4% rapid acetylators and 35.6% slow acetylators according to bimodal distribution. Frequencies of NAT2 alleles for the Indonesian population resemble those of other Southeast Asian populations
medicine
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ocular defects associated with a null mutation in the mouse arylamine N-acetyltransferase 2 gene
medicine
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polymorphisms of arylamine N-acetyltransferase 2 are reportedly associated with the risk of drug toxicities and development of various diseases such as cancer and neurodegenerative diseases
medicine
present study examines an association of slow N-acetyltransferase 2 profile caused by classical N-acetylation polymorphism and anti-tuberculosis drug-induced hepatotoxicity in patients from Southern Brazil. 254 Brazilian tuberculosis patients using isoniazid (INH), rifampicin (RMP), and pirazinamide (PZA) are tested in a prospective cohort study. Results demonstrate that HIV-positive patients that have the slow acetylation profile are significantly associated with a higher risk of developing hepatotoxicity due to anti-tuberculosis drugs
medicine
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results show that DNA hypomethylation in the NAT1 gene is present in cancerous breast tissues thus indicating that this type of methylation may significantly influence the transcriptional activation of the gene. Therefore, hypomethylation of the NAT1 gene plays a significant role in breast carcinogenesis
medicine
results show that human NAT1 is induced by androgens, which may have implications for cancer risk in individuals
medicine
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results show that Warburgia salutaris is a useful source of anti-tubercular compounds for further analysis and supports the hypothesis of a link between NAT inhibition and antimycobacterial activity
medicine
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results show that Warburgia salutaris is a useful source of anti-tubercular compounds for further analysis and supports the hypothesis of a link between NAT inhibition and antimycobacterial activity
medicine
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results suggest that care should be taken to prevent the development of isoniazid-induced hepatic disorder in patients who have the NAT2 SA phenotype, a high concentration of rifampicin and who carry the GST M1 null genotype
medicine
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TBNAT remains a potential drug target for the treatment of tuberculosis
medicine
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the data pave the way for investigating NAT1 transcripts as candidate prognostic markers in ER-positive breast cancer
medicine
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the evaluation of the NAT2 gene in Brazilians subjects demonstrated a considerable prevalence of slow acetylatots and established a basis for further investigations
medicine
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the findings show that inflammation can supress NAT1, a key cellular defense enzyme, such a suppression may be implicated in drug toxicity and cancer risk
medicine
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the internationally recommended dosage of isoniazid for patients with two active NAT2 alleles in order to achieve appropriate antituberculous efficiency should be increased
medicine
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the present data do not support a relevant impact of the NAT1 genotype on colorectal cancer risk development in the study area
medicine
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the results suggest that the irreversible inactivation of NAT1 by cysplatin may at least partly contribute to the pharmacological and, or toxicological effects of cisplatin
medicine
there is increasing evidence that arylamine N-acetyltransferases could contribute to antibiotic resistance in pathogenic bacteria
medicine
to better understand the possible relationship between the NAT2 gene and endometriosis, its homologue in the resus macaque is characterized
medicine
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to estimate an optimal dosage for isoniazid (INH) RA-type patients (patients with two active NAT2 alleles due to genetic polymorphisms) a dose escalation study in healthy male volunteers is conducted carrying mutation NAT2*4/*4. In RA-type subjects, the pharmacokinetic parameters appear to lack linearity with the increased dose of isoniazid. It is proposed that the proper daily dose for RA-type patients is 1.5times higher than that currently recommended
medicine
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tobacco smoking is shown to change the risk significance of individual alleles NAT2 to predisposition to multifactor diseases
medicine
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Warburgia salutaris is a useful source of anti-tubercular compounds for further analysis and supports the hypothesis of a link between NAT inhibition and anti-mycobacterial activity
medicine
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co-expression of Escherichia coli nitroreductase and arylamine N-acetyltransferase NAT2 in SKOV3 cells decreases the IC50 value of prodrug CB1954, i.e. 5-(aziridin-1-yl)-2,4-dinitrobenzamide, 16fold. The significantly decreased bystander effect may provide a greater clinical response at therapeutic concentrations of CB1954
medicine
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exposure of lung epithelial cells to pathophysiologically relevant amounts of oxidants such as H2O2 or peroxyntrite, impairs the Nat1-dependent cellular biotransformation of aromatic amines
medicine
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exposure of lung epithelial cells to pathophysiologically relevant amounts of oxidants such as H2O2 or peroxyntrite, impairs the Nat2-dependent cellular biotransformation of aromatic amines
medicine
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increasing acetylation by introduction of the human NAT1 transgene is protective against sporadic dilantin-induced orofacial clefting defects in the mouse A/J strain
medicine
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knock-down of enzymeby lentiviral shRNA reduces the invasion potential of MDA-MB-231 cells. Enzymic activity may be important in breast cancer growth and metastasis
medicine
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knockout of NAT2 significantly decreases teratogen-induced orofacial clefting in the A/J strain, but not in the C57BL/6J strain
medicine
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presence of *12A and the absence of *12B, *13, *14B, *14D, *6A, and *7A NAT2 haplotypes are risk factors for differentiated thyroid cancer. The inheritance of a rapid acetylation phenotype doubles the risk for a papillary carcinoma. No relationship between genotypes and clinical, pathologic, or laboratory features of patients or between genotypes and outcome
medicine
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enzyme expression is correlated with improved overall survival of breast cancer patients. The enzyme is a possible prognostic biomarker for lymph node-positive breast cancer
medicine
a negative correlation is found between the expression of NAT1 and MMP9 in 1904 breast cancer samples
medicine
isoniazid N-acetylation rates in vitro exhibit a robust and highly significant NAT2 phenotype-dependent metabolism. N-acetylation rates in situ are isoniazid concentration- and time-dependent. Following incubation for 24 h with 12.5 or 100 mmol/l isoniazid, acetyl-isoniazid concentrations vary significantly across cryopreserved human hepatocytes samples from rapid, intermediate, and slow acetylators, respectively. N-acetylation rates of N-(4-aminobenzoyl)-L-glutamate in vitro do not differ significantly between rapid, intermediate, and slow NAT2 acetylators. N-acetylation rates towards isoniazid in the identical samples exhibit a robust and highly significant NAT2 genotype-dependent metabolism
medicine
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loss of NAT1 in in MDA-MB-231, HT-29 and HeLa cells increases adherence to collagen but migration of cells is unaffected. NAT1 deletion decreases invasion and induces changes to cell morphology. These effects are independent of matrix metalloproteinases but are related to integrin ITGalphaV expression
medicine
MOCA N-acetylation exhibits a robust gene dose response in cryopreserved human hepatocytes derived from individuals of rapid, intermediate and slow acetylator NAT2 genotype. 4,4'-methylenebis(2-chloroaniline)(MOCA) exhibits about 4fold higher affinity for recombinant human NAT2 than NAT1. Recombinant human NAT2 4 (reference) and 15 variant recombinant human NAT2 allozymes catalyze both the N-acetylation of MOCA and the O-acetylation of N-hydroxy-MOCA. Human NAT2 5, NAT2 6, NAT2 7 and NAT2 14 allozymes catalyze MOCA N-acetylation and N-hydroxy-O-acetylation at rates much lower than the reference NAT2 4 allozyme
medicine
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there is no association between phenotypes of NAT2 polymorphisms and breast cancer. Ethnic and geographic differences in NAT2 polymorphism are present, but not associated with the risk of breast cancer in general. Intermediate acetylator is protective for particular ethnic groups
molecular biology
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results demonstrate that human P4501A1 and NATs (NAT1 and NAT2) contribute significantly to the activation of PBTA-type compounds to genotoxic metabolites that induce umuC gene expression in Salmonella typhimurium tester strains
molecular biology
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results show that cisplatin inactivates the NAT1 enzyme by forming an adduct with the catalytic cysteine residue of the enzyme
molecular biology
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results show that cisplatin inactivates the NAT1 enzyme by forming an adduct with the catalytic cysteine residue of the enzyme
pharmacology
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arylamine N-acetyltransferases have a key role in the detoxication and metabolic activation of numerous xenobiotics, including therapeutic drugs and carcinogens
pharmacology
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NATs play an important role in the detoxication and, or bioactivation of numerous drugs and xenobiotics