Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Berberine is an alkaloid occurring in the plant genera Berberis and Coptis. Although berberine had been demonstrated to have antineoplastic function by inhibiting DNA-synthesis in activated lymphocytes, there is no available information to address berberine affects on human leukemia cell N-acetyltransferase (NAT) activity and 2-aminofluorene (AF)-DNA adduct formation. Thus, berberine was tested for inhibition of arylamine NAT activity and AF-DNA adduct formation in human leukemia cells. The NAT activity was measured by a high performance liquid chromatography assaying for the amounts of N-acetyl-2-aminofluorene (AAF) and N-acetyl-p-aminobenzoic acid (N-Ac-PABA) and the remaining AF and p-aminobenzoic acid (PABA). The NAT activity and AF-DNA adduct formation in human leukemia cells were inhibited by berberine in a dose-dependent manner, i.e. the higher the concentration of berberine, the higher the inhibition of NAT activity and AF-DNA adduct. The data also indicate that berberine decreased the apparent values of Km and Vmax from human leukemia cells in both cytosol and intact cells.
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PMID:Effects of berberine on arylamine N-acetyltransferase activity and 2-aminofluorene-DNA adduct formation in human leukemia cells. 1099 41

N-Acetyltransferase enzyme is an important enzyme in the first step of arylamine compounds metabolism. Luteolin has been shown to exit antibacterial and antineoplastic activity. The purpose of this present study is to evaluate the question of whether luteolin could affect arylamine N-acetyltransferase (NAT) activity and DNA-2-aminofluorene adduct formation in human (HL-60) and mouse (L1210) leukemia cells. By using HPLC, N-acetylation of 2-aminofluorene was determined. Luteolin displayed a dose-dependent inhibition to cytosolic NAT activity and intact human and mice leukemia cells. Time-course experiments showed that N-acetylation of 2-aminofluorene measured from intact human and mice leukemia cells were inhibited by luteolin for up to 24 hours. Using standard steady-state kinetic analysis, it was demonstrated that luteolin was a possible uncompetitive inhibitor to NAT activity in cytosols. The DNA-2-aminofluorene adduct formation in human and mouse leukemia cells were inhibited by luteolin. This report is the first demonstration to show that luteolin affects human and mice leukemia cells NAT activity and DNA-2-aminofluorene on adduct formation.
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PMID:Luteolin-inhibited arylamine N-acetyltransferase activity and DNA-2-aminofluorene adduct in human and mouse leukemia cells. 1139 11

N-Acetylation is recognized as the first step in arylamine metabolism. The enzyme responsible for N-acetylation is called arylamine N-acetyltransferase (NAT),which uses acetyl coenzyme A as the acetyl group donor. Paclitaxel has been shown to exhibit antineoplastic and anticancer activity. In this study, paclitaxel was selected to determine the inhibition of arylamine N-acetyltransferase activity, gene expression (NAT mRNA) and DNA-2-aminofluorene adduct formation in human leukemia HL-60 cell line. Paclitaxel (0.01-l microM) did decrease the level of NAT mRNA in a dose-dependent manner. The results demonstrated that paclitaxel inhibited NAT activity and DNA-2-aminofluorene adduct formation in human leukemia HL-60 cells in a dose-dependent manner. Using standard steady-state kinetic analysis, it was demonstrated that paclitaxel was a possible uncompetitive inhibitor to NAT activity in cytosols based on the decrease in apparent values of K(m) and V(max). This report is the first demonstration that paclitaxel affected human leukemia HL-60 cells NAT activity and DNA-2-aminofluorene adduct formation.
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PMID:The effect of paclitaxel on gene expression and activity of arylamine N-acetyltransferase and DNA-2-aminofluorene adduct formation in human leukemia HL-60 cells. 1195 77

Electric and magnetic fields are associated with the production, transmission, and use of electricity; thus the potential for human exposure is high. These electric and magnetic fields are predominantly of low frequency (60 Hz) and generally of low intensity. The prevailing view among physicists is that exposure to these low-frequency, low-intensity fields does not pose a health hazard. However, this view has been challenged by reports linking magnetic field exposure to the development of leukemia and other cancers. Because multiple epidemiologic studies suggested a potential for increased cancer rates with increasing exposure, and because of public concern, the effects of 60-Hz magnetic field exposure were examined in F344/N rats and B6C3F1 mice in 8-week full-body-exposure studies. Animals were evaluated for hematology and clinical chemistry (rats only) parameters, pineal gland hormone concentrations, and histopathology. Additional studies were performed in Sprague-Dawley rats to examine teratologic and reproductive effects of magnetic field exposure. In the 8-week toxicity studies, groups of male and female F344/N rats and B6C3F1 mice were exposed for 18.5 hours per day to 60-Hz magnetic fields at intensities of 0 (control), 0.02, 2, and 10 gauss (G). Additional groups of rats and mice were exposed to intermittent 10 G fields (1 hour on/1 hour off) for 18.5 hours per day. No evidence of toxicity associated with exposure to magnetic fields was observed in rats or mice. Clinical observations provided no evidence of adverse effects associated with magnetic field exposure. Compared to control rats and mice, there were no biologically significant differences in hematology or clinical chemistry parameters of rats exposed to magnetic fields. No gross lesions or histopathologic findings in rats or mice were attributed to exposure to 60-Hz magnetic fields. In addition, magnetic field exposure was not associated with a significant reduction in serum melatonin or pineal gland melatonin concentration, or pineal gland activity of N-acetyltransferase in either species. One female rat in the 2 G exposure group died during the 8-week toxicity study from causes unrelated to magnetic field exposure; all other male and female rats and mice in the study survived until the end of the study. Final mean body weights and mean organ weights of a few groups of exposed animals differed from those of the control groups; however, no clear pattern of magnetic field effects was observed, and these differences are not considered to be biologically significant. For the teratology study, groups of 55 pregnant female Sprague-Dawley rats were exposed to the same magnetic fields as in the toxicity study on gestation days 6 through 19. Fifteen pregnant females exposed to 85 mg ethylenethiourea/kg body weight served as positive controls. Except for the positive controls, there were no changes in maternal or fetal weights, nor were fetal abnormalities found. The number of pregnant females was significantly lower in groups exposed to magnetic fields than in the control group; however, all breeding in the teratology study was completed prior to the first day of magnetic field or sham exposure. On this basis, this finding is unrelated to magnetic field exposure. In addition, there were no differences between control and exposed groups in the number of pregnant females in the continuous breeding study, in which breeding took place within the magnetic fields. Groups of 40 breeding pairs of Sprague-Dawley rats were exposed to the same magnetic fields as in the toxicity study during the breeding and lactation of five litters in a continuous breeding study. The fifth litter was exposed during gestation and lactation; one male and one female from each litter were raised to sexual maturity receiving the same exposures as the parents; rats were mated to nonsibling rats and allowed to deliver the third-generation offspring. The results of the continuous breeding study demonstrated no effects of magnetic field exposure on reproductive performance in either male or female rats.
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PMID:NTP Toxicity Studies of 60-Hz Magnetic Fields Administered by Whole Body Exposure to F344/N Rats, Sprague-Dawley Rats, and B6C3F1 Mice. 1198 81

Two components of garlic, diallyl sulfide (DAS) and diallyl disulfide (DADS), inhibited arylamine N-acetyltransferase (NAT) activity and 2-aminofluorene-DNA adduct in human promyelocytic leukemia cells (HL-60). The NAT activity was measured by high performance liquid chromatography assaying for amounts of N-acetyl-2-aminofluorene (2-AAF) and remaining 2-aminofluorene (2-AF). Cellular cytosols and intact cell suspensions were assayed. The inhibition of NAT activity and 2-AF-DNA adduct formation in human leukemia cells by DAS and DADS were dose-dependent and were directly proportional. The data also indicated that DAS and DADS decrease the apparent values of Km and Vmax from human leukemia cells in both assays. This is the first report of garlic components affecting human leukemia cell NAT activity and 2-AF-DNA adduct formation.
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PMID:Effects of garlic components diallyl sulfide and diallyl disulfide on arylamine N-acetyltransferase activity and 2-aminofluorene-DNA adducts in human promyelocytic leukemia cells. 1223 20

N-Acetyltransferases (NATs) plays an important role in the first step of arylamine compounds metabolism. Polymorphic NAT is coded for rapid or slow acetylatoion phenotypes, which are recognized to affect cancer risk related to environmental exposure. Aloe-emodin has been shown to exit anticancer activity. The purpose of this study is to examine whether or not aloe-emodin could affect arylamine N-acetyltransferase (NAT) activity and gene expression (NAT mRNA) and DNA-2-aminofluorene (DNA-AF) adduct formation in mouse leukemia cells (L 1210). By using high performance liquid chromatography, N-acetylation and non-N-acetylation of AF were determined and quantitated. By using reverse transcriptase-polymerase chain reaction (RT-PCR) and PCR, NAT mRNA was determined and quantitated. Aloe-emodin displayed a dose-dependent inhibition to cytosolic NAT activity and intact mice leukemia cells. Time-course experiments indicated that N-acetylation of AF measured from intact mice leukemia cells were inhibited by aloe-emodin for up to 24h. Using standard steady-state kinetic analysis, it was demonstrated that aloe-emodin was a possible uncompetitive inhibitor to NAT activity in cytosols. The DNA-AF adduct formation in mouse leukemia cells were inhibited by aloe-emodin. The NAT1 mRNA in mouse leukemia cells were also inhibited by aloe-emodin. This report is the first demonstration which showed aloe-emodin affect mice leukemia cells NAT activity, gene expression (NAT1 mRNA) and DNA-AF on adduct formation.
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PMID:Aloe-emodin inhibited N-acetylation and DNA adduct of 2-aminofluorene and arylamine N-acetyltransferase gene expression in mouse leukemia L 1210 cells. 1280 42

Genetic regulation of acetyl coenzyme A-dependent N-acetyltransferase (NAT)and O-acetyltransferase (OAT) activities may play an important role in the metabolic activation of arylamine chemicals and carcinogens. N-acetylation is thought to be the first step in arylamine metabolism. The enzyme responsible for N-acetylation is called NAT. In this study, synthetic non-steroidal antiestrogen tamoxifen was selected for determining the inhibition of arylamine NAT activity, gene expression (NAT mRNA) and DNA-2-aminofluorene adduct formation in human leukemia HL-60 cell line. The results demonstrated that tamoxifen did not affect the level of NAT mRNA in HL-60 cells. But the results also showed that NAT activity and 2-Aminofluorene-DNA adduct formation in HL-60 cells were inhibited and decreased by tamoxifen in a dose-dependent manner when the doses of tamoxifen up to 100 micro M. We also examined the standard steady-state kinetic analysis, and the data showed that tamoxifen may be an uncompetitive inhibitor to NAT activity in cytosols based on the decrease apparent values of Km and Vmax. This report is the first finding that tamoxifen inhibited human leukemia HL-60 cells NAT activity and DNA-2-aminofluorene on adduct formation.
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PMID:Tamoxifen inhibits arylamine N-acetyltransferase activity and DNA-2-aminofluorene adduct in human leukemia HL-60 cells. 1288 15

Approximately 10% of newborns with Down syndrome develop Transient Leukemia (TL), a disorder that is unique to infants with constitutional trisomy 21 (or trisomy 21 mosaicism). TL blasts disappear spontaneously within the first 3 months of life in the majority of cases. Despite the resolution of TL, 20-30% of these newborns will go on to develop acute megakaryoblastic leukemia (AMKL) later in life. In this study, samples from both TL and AMKL patients were examined using cDNA microarrays to study the pathogenic progression from TL to AMKL. TL and AMKL samples partition separately by cluster analysis, and AMKL samples had substantial increases in apolipoprotein C-I, transporter 1, myosin alkali light chain 4, and spermidine/spermine N-acetyltransferase, compared to TL samples. Although these findings will require validation in an independent series of TL and AMKL samples, they indicate that TL and AMKL have distinct gene signatures, and provide a basis for studies of the different mechanisms underlying either the resolution of TL or its progression to AMKL.
Leukemia 2004 Oct
PMID:Distinct gene signatures of transient and acute megakaryoblastic leukemia in Down syndrome. 1534 46

Many arylamine and hydrazine drugs are acetylated by cytosolic N-acetyltransferase (NAT). The human promyelocytic leukemia cell line (HL-60) has been shown to acetylate arylamine and contain NAT activity. The purpose of this study was to determine whether or not baicalein could affect N-acetylation of 2-aminofluorene (AF) in HL-60 cells. Acetylated and nonacetylated AF were determined by using high performance liquid chromatography. Baicalein displayed a dose-dependent inhibition of cytosolic and intact cells' NAT activity and reduced the number of viable cells. Time-course experiments showed that N-acetylation of AF, measured from intact HL-60 cells, was inhibited by baicalein for up to 48 h. Baicalein also decreased AF-DNA adduct formation in the examined cells. The effects of baicalein on NAT were examined by flow cytometry and NAT gene expression was examined by polymerase chain reaction. The results demonstrated that baicalein inhibited NAT1 mRNA gene expression and reduced the level of NAT in HL-60 cells. These results show that baicalein can affect the NAT activity of human leukemia cells in vitro.
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PMID:N-acetyltransferase is involved in baicalein-induced N-acetylation of 2-aminofluorene and DNA-2-aminofluorene adduct formation in human leukemia HL-60 cells. 1579 4

It is well documented that arylamine carcinogens are N-acetylated by cytosolic N-acetyltransferase (NAT) enzyme. NAT plays an important role in the metabolizing of those arylamine compounds. 2-Aminofluorene (AF) is an arylamine carcinogen which has been demonstrated to induce carcinogenesis in laboratory animals. Our previous study has shown that a human promyelocytic leukemia cell line, HL-60, displays NAT activity. The purpose of the present study was to determine whether or not wogonin could affect the N-acetylation of AF in HL-60. N-acetylated and non-N-acetylated AF were determined by using high performance liquid chromatography. Wogonin displayed a dose-dependent inhibition of NAT activity in cytosols and intact cells. Wogonin also decreased AF-DNA adduct formation in these cells. The effects of wogonin on the NAT enzymes levels were also examined by Western blotting and flow cytometry and the changes of NAT gene expression were examined by polymerase chain reaction (PCR) and cDNA microarray. The results demonstrated that wogonin inhibited NAT1 mRNA gene expression and the level of NAT enzyme in HL-60 cells. This is the first demonstration that wogonin affects human leukemia cells' NAT activity in vitro.
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PMID:Wogonin inhibits N-acetyltransferase activity and gene expression in human leukemia HL-60 cells. 1581 29


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