Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Whether single cells immunohistochemically positive for glutathione S-transferase P1-1 (GSTP1-1) induced in the female mouse liver by DEN (Hatayama et al., Carcinogenesis, 14, 537-538, 1993) are precursor initiated cells of preneoplastic foci, is of importance in chemical hepatocarcinogenesis. Nrf2 transactivates a wide variety of ARE (anti-oxidant response element)-mediated enzymes including GSTP1-1. Quantitative examination revealed that the basal expression of hepatic GSTP1-1 was 60% lower in Nrf2 gene knock-out female mice(-/-) than in wild type females, and that treatment with butyrated hydroxyanisole (BHA) increased by 10-fold GSTP1-1 expression in the liver of wild type female mice but not in knockout female mice(-/-). Despite the lack of Nrf2, GSTP1-1-positive single cells were detected in livers of DEN-treated female(-/-) 3 months after treatment. Subsequent BHA feeding to the positive cell-bearing females for one more week clearly showed that the single cells were detectable with females(-/-) but not with females(+/+,+/-) due to the strong induction of GSTP1-1 in the surrounding hepatocytes. The sensitivity to DEN hepatocarcinogenesis was not significantly different among genotypes. These results demonstrate that Nrf2 is regulatory in normal hepatocytes but not in the single cells positive for GSTP1-1 inducible in the female mouse liver by DEN. The transcriptional distinction observed for the DEN-transformants is suggestive of a preneoplastic character of precursor initiated cells.
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PMID:Nrf2 transactivator-independent GSTP1-1 expression in "GSTP1-1 positive" single cells inducible in female mouse liver by DEN: a preneoplastic character of possible initiated cells. 1189 60

To determine whether interferon alfa (IFN-alpha) prevents in vivo oncogenesis in very-early-stage cancer cells, we evaluated the action of IFN-alpha2b over preneoplastic foci in rats. Animals were divided into 6 groups: subjected to a 2-phase model (diethylnitrosamine [DEN] plus 2-acetylaminofluorene [2-AAF]) of preneoplasia development (group 1), treated with IFN-alpha2b during the 2 phases (group 2), only during initiation with DEN (group 3), only during administration of 2-AAF (group 4), subjected only to an initiation stage (group 5), and treated with IFN-alpha2b during this period (group 6). The numbers of placental form of rat glutathione S-transferase (rGST-P)-positive foci per liver and the foci as percentage of liver were significantly reduced in groups 2, 3, and 6 but not in group 4. Rats treated with IFN-alpha2b showed a higher apoptotic index (AI) in altered hepatic foci (AHF). Levels of p53 and Bax protein in liver lysates were significantly increased in those animals. Similarly, levels of antiapoptotic proteins Bcl-2 and Bcl-x(L) in mitochondrial fraction were decreased. Finally, increased levels of Bax protein were localized in the mitochondria of rats that received IFN-alpha2b, at least during the DEN phase (groups 2, 3, and 6), whereas mitochondrial Bax expression was not increased in group 4. In conclusion, the preneoplastic hepatocytes in rats that received IFN-alpha2b during the initiation stage undergo programmed cell death as a primary result of a significant increase in the amount and translocation to the mitochondria of Bax protein.
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PMID:The in vivo apoptotic effect of interferon alfa-2b on rat preneoplastic liver involves Bax protein. 1191 28

The effect of chronic administration of 0.002% N-nitrosodiethylamine (DENA), 0.002% diethylamine (DEA) and 0.0005% sodium nitrite (SN) on the functional state of the xenobiotic metabolizing system in rat liver was investigated. Administration of DEA and DENA increased concentration of cytochromes P-450 and b5. SN did not affect the enzymes of the monooxygenase system. Coadministration of DEA and SN maximally increased the concentration of cytochrome P-450. It is not possible to explain the phenomenon of combined administration of SN and DEA by simple summation of the effects caused by them separately. The activity of microsomal glutathione S-transferase did not change when DEA and SN were given together, yet increased when they were administered separately. The maximum increase of the total activity of cytosol glutathione S-transferases was observed following DENA. In all four experimental groups a decrease of isoenzyme 5-5 activity was observed. Investigation of Se-independent glutathione peroxidase activity showed the multivariance of response of the glutathione S-transferase family to the compounds studied. The concentration of hepatic free SH-groups increased following administration of DENA and decreased dramatically when SN and DEA were coadministered. When they were given separately the concentration remained at control level.
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PMID:The functional state of the xenobiotic metabolizing system in rat liver following chronic administration of diethylnitrosamine or its precursors. 1237 41

The dietary administration of selenium (sodium selenite; 4 p.p.m.) daily has been found to be highly effective in reducing the incidence of cancer induced by N-nitrosodiethylamine (DEN) in Wistar strain rats. Selenium treatment either before initiation, during initiation and selection/phenobarbital promotion phases of hepatocarcinogenesis has been found to be effective in elevating hepatic microsomal cytochrome b(5), NADPH-cytochrome C reductase and cytosolic aryl hydrocarbon hydroxylase activities to a statistically significant level measured either in the hyperplastic nodule or in the surrounding liver tissues compared to control animals. Moreover, selenium treatment throughout the study, decreases the cytosolic glutathione S-transferase and microsomal UDP-glucuronyl transferase activities by a significant degree when compared to control rats. Alterations in glutathione metabolizing enzyme activities (glutathione reductase, gamma-glutamyl transpeptidase, gamma-glutamylcysteine synthetase and glucose-6-phosphate dehydrogenase) were also observed in selenium-treated groups. Our results confirm the fact that selenium is particularly protective in limiting the action of DEN during the initiation phase of hepatocarcinogenesis.
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PMID:Dietary influence of selenium on the incidence of N-nitrosodiethylamine-induced hepatoma with reference to drug and glutathione metabolizing enzymes. 1241 70

Feeding menhaden oil, high in n-3 fatty acids, or a mixture of lard and corn oil with a polyunsaturated-to-monounsaturated fatty acid ratio of 1:1 was hypothesized to inhibit promotion of hepatocarcinogenesis in rats by decreasing hepatic prostaglandin (PG) levels. Ten-day-old female Sprague-Dawley rats were injected with diethylnitrosamine (DEN, 15 mg/kg body wt ip). At 4 wk of age, rats were fed fumonisin B1(50 mg/kg diet) for 5 wk in diets containing 14% lard + 6% corn oil, 10% lard + 10% corn oil, 14% menhaden oil + 6% corn oil, and 7% menhaden oil + 13% corn oil. Plasma alanine aminotransferase activity was 20% lower in rats fed 10% lard than in rats fed the other diets (P < 0.05). In menhaden oil-fed rats, total plasma cholesterol concentrations decreased 26% (P < 0.05) and hepatic phospholipid C20:5n-3, C22:5n-3, and C22:6n-3 fatty acid concentrations increased compared with lard-fed rats. Hepatic n-3 fatty acids were threefold greater in rats fed 10% lard than in rats fed 14% lard. The liver-associated natural killer cell activity in rats fed menhaden oil was 58% lower than in rats fed lard (P < 0.03). Rats fed lard had threefold (P < 0.05) greater area of _-glutamyltransferase-positive altered hepatic foci (AHF) than did rats fed menhaden oil. There was no significant difference in placental glutathione S-transferase-positive AHF among the groups. Hepatic PGF2alpha production was 60-80% greater in rats fed 14% lard than in rats fed the other diets (P < 0.05). Hepatic PGE2 was 48% less in rats fed 14%; menhaden oil than in rats fed 14% lard (P < 0.05). Although gamma-glutamyltransferase-positive focal area was inhibited by menhaden oil, only 14% menhaden oil inhibited PGE2. Feeding 10% lard inhibited PGF2alpha, but not the development of AHF. Therefore, decreased hepatic PGs did not explain the inhibition of carcinogenesis.
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PMID:Menhaden oil inhibited gamma-glutamyltransferase-positive altered hepatic foci in female Sprague-Dawley rats. 1267 44

The chemopreventive potential of an Agaricus blazei (Ab) Murrill mushroom meal was investigated in a medium-term rat liver carcinogenesis assay. Male Wistar rats initiated for hepatocarcinogenesis with diethylnitrosamine (DEN, 200 mg/kg i.p.) were fed during a 6-week period with the dry powdered mushroom strains Ab 29 or 26, each one with opened (OB) or closed basidiocarp (CB), mixed at 10% level in a basal diet. All experimental animals and controls were subjected to partial hepatectomy at week 3 and killed at week 8. Chemopreventive activity of the mushroom meal was observed for the Ab 29 (OB and CB) and Ab 26 (CB) strains in terms of the number of putative preneoplastic altered foci of hepatocytes which express either the enzyme glutathione S-transferase, placental form (GST-P+) or the transforming growth factor-alpha, and for the Ab 29 (OB) and Ab 26 (CB) strains on the size of GST-P+ foci. This was associated with inhibition of foci cell proliferation in the animals fed the Ab 29 (OB) and Ab 26 (CB) strains. The results suggest that the protective influence of the Ab meal against the DEN potential for rat liver carcinogenicity depends on both the strain and period of mushroom harvest.
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PMID:Chemoprevention of preneoplastic liver foci development by dietary mushroom Agaricus blazei Murrill in the rat. 1296 7

This study was conducted to examine the effects of dietary grape extracts on preneoplastic foci formation in rat hepatocarcinogenesis, and related hepatic enzymes. Male Sprague-Dawley rats were fed basal diet or grape diet containing 15% concentrated grape extracts (68 bricks). The grape diet groups were divided into whole-period grape diet group (DEN-GW; grape diet group fed throughout experimental period) and postinitiation grape diet group (DEN-GP; grape diet group fed from post initiation stage) according to the starting time point of the grape diet. Hepatocarcinogenesis was induced by diethylnitrosamine (DEN; 200 mg/kg bw) and 2/3 partial hepatectomy (DEN-B; DEN-treated basal diet group, DEN-GW, and DEN-GP groups), while the control group treated with saline and sham operation (Control group). The formation of placental glutathione (GSH) S-transferase positive (GST-P+) foci in DEN-GW group was moderately but significantly suppressed, however, not in DEN- GP group. Thiobarbituric acid reactive substances content of DEN-GW group was significantly lower than that of DEN-B group. The activity of fatty acid synthase (FAS) in the grape diet groups was decreased about 1/2 of the DEN-B group. The content of GSH and GSH peroxidase activity were increased by carcinogen treatment, but not modulated by grape diet. The activities of GSH S-transferase, p-nitrophenol hydroxylase, and catalase were not affected by diet or treatment. Conclusively, the grape diet-induced reduction of FAS activity that was expressed highly in neoplastic tissues, might be one of the contributing mechanisms of hepatic cancer prevention.
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PMID:Grape extracts suppress the formation of preneoplastic foci and activity of fatty acid synthase in rat liver. 1464 90

Annatto (Bixa orellana L.) is a natural food colorant extensively used in many processed foods, especially dairy products. The lower cost of production and the low toxicity, make annatto a very attractive and convenient pigment in substitution to the many synthetic colorants. In the present study we investigate the carcinogenic and anticarcinogenic effects of dietary annatto in Wistar rat liver using the preneoplastic glutathione S-transferase (GST-P) foci and DNA damage biomarkers. Annatto, containing 5% bixin, was administered in the diet at concentrations of 20, 200, and 1000 ppm (0.07; 0.80 and 4.23 bixin/kg body wt/day, respectively), continuously during 2 weeks before, or 8 weeks after DEN treatment (200 mg/kg body wt, i.p.), to evaluate its effect on the liver-carcinogenesis medium-term bioassay. The comet assay was used to investigate the modifying potential of annatto on DEN (20 mg/kg body wt)-induced DNA damage. The results showed that annatto was neither genotoxic nor carcinogenic at the highest concentration tested (1000 ppm). No protective effects were also observed in both GST-P foci development and comet assays. In conclusion, in such experimental conditions, annatto shows no hepatocarcinogenic effect or modifying potential against DEN-induced DNA damage and preneoplastic foci in the rat liver.
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PMID:Absence of carcinogenic and anticarcinogenic effects of annatto in the rat liver medium-term assay. 1535 20

The chemopreventive effect of ethanol extract of Indigofera aspalathoides (EIA) on N-nitrosodiethylamine (DEN, 200 mg/kg)-induced experimental liver tumor was investigated in male Wistar rats. Oral administration of ethanol extract of Indigofera aspalathoides (250 mg/kg) effectively suppressed liver tumor induced with DEN as revealed by decrease in the levels of extend of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin, gamma glutamate transpeptidase (GGTP), lipid peroxidase (LPO), glutathione peroxidase (Gpx) and glutathione S-transferase (GST) with a concomitant increase in enzymatic antioxidant (superoxide dismutase and catalase) levels when compared to those in liver tumor bearing rats. The histopathological changes of liver sample were compared with respective control. Our results show a significant chemopreventive effect of EIA against DEN induced liver tumor.
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PMID:Chemoprevention of N-nitrosodiethylamine induced phenobarbitol promoted liver tumors in rat by extract of Indigofera aspalathoides. 1568 1

Regulation of cell proliferation and apoptosis plays a key role in tumor development. To elucidate mechanisms underlying hepatocarcinogenesis, patterns of gene expression, including apoptosis-related genes, were compared between glutathione S-transferase placental form (GST-P)-positive preneoplastic foci and surrounding tissue in the rat. Lesions were induced with a single intraperitoneal injection of diethylnitrosamine (DEN, 200 mg/kg bw) and then 100 ppm 2-acetylaminofluorene (2-AAF)-containing diet combined with two-thirds partial hepatectomy. Frozen sections of the livers were applied for immunohistochemical staining of GST-P, and both positive foci and surrounding negative areas were harvested by laser microdissection. Total RNAs were extracted and amplified with T7 polymerase to allow gene expression analysis by cDNA microarray assays. In the GST-P-positive foci, altered levels were observed for many genes, mostly related to metabolism or catalysis, with increased expression of testosterone-repressive prostate message-2 (TRPM-2), which is reported to act as a protective factor against apoptosis, and decreased expression of thymus-expressed acidic protein (TEAP), which is considered to promote apoptosis. The results indicate that rat liver preneoplastic lesions might be protected against apoptosis and that the approach adopted is useful for clarification of mechanisms underlying hepatocarcinogenesis.
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PMID:Downregulation of apoptosis revealed by laser microdissection and cDNA microarray analysis of related genes in rat liver preneoplastic lesions. 1615 76


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