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)

Using the polymerase chain reaction (PCR), a human kidney glutathione S-transferase (GST) alpha cDNA clone (GST alpha 12 K) was synthesized; it is identical to a known liver GST alpha cDNA clone except for one base change (G----A), indicating that an alpha class gene expressed in human kidney is similar to one expressed in human liver. Comparisons were made in the expression of GST alpha and GST pi between renal cell carcinoma and adjacent non-neoplastic tissue. Messenger RNA expression in 30 cases was determined by Northern blotting, and GST protein from nine of these cases was analyzed by HPLC. The GST alpha gene products were expressed at near-zero levels. The GST pi gene product was the predominant GST in tumors, but was decreased in absolute amount compared with control tissue, the tumor/control ratios for the GST pi gene obtained by Northern blots and HPLC analysis being 0.50 +/- 0.07 and 0.36 +/- 0.07 respectively. The resulting pattern in renal cell carcinoma therefore shows a predominance of GST pi. Since it is assumed that renal cell carcinoma derives from the proximal tubular epithelial cells which are high in GST alpha, this implies a dedifferentation in the GST expression pattern.
Carcinogenesis 1990 Dec
PMID:Decreased expression of the glutathione S-transferases alpha and pi genes in human renal cell carcinoma. 226 70

The modifying effects of harman or norharman on liver carcinogenesis were investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given harman or norharman at dietary levels of 1000 and 200 parts per million (ppm), or sodium phenobarbital (PB) at 500 ppm as a positive control, for 6 wk. At wk 3 following DEN administration, all animals were subjected to partial hepatectomy. Marked retardation of body weight gain was observed in rats treated with harman or norharman at 1000 ppm, but not at 200 ppm. Increased relative kidney but not liver weights were associated with harman or norharman treatment, especially in the higher dose groups. Although no toxicity-related hepatocyte lesions were found, severe renal toxic tubular lesions and regeneration were evident. Neither harman nor norharman significantly increased the numbers or areas of glutathione S-transferase placental form (GST-P) positive foci observed after DEN initiation, in clear contrast to PB. The results thus demonstrated that harman and norharman are nontoxic for the liver and lack modifying potential for liver carcinogenesis in our medium-term bioassay system.
 ...
PMID:Lack of hepatotoxicity or promotion of enzyme-altered liver foci development in rats treated with harman or norharman. 229 94

The levels of glutathione S-transferase (GST) isoenzymes, GST pi, B1, B2 and mu were measured, by radioimmunoassay, in human bronchoalveolar lavage fluid from a series of patients presenting with neoplastic (n = 12) and non-neoplastic lung diseases (n = 10). Lavage fluid was obtained from the suspected abnormal area of lung and a presumed normal area of lung at the time of bronchoscopy. Concentrations of GST B1 and GST B2 were found to be significantly raised (P less than 0.02) in the lavage fluid obtained from the suspected abnormal areas of lung compared with the presumed normal area of lung, in patients later diagnosed as having cancer of the bronchus. The findings of the radioimmunoassay, of greater levels of GST B1 and B2 than GST pi in lavage fluid, were confirmed by a one-step purification of GST from lung lavage, using affinity chromatography, followed by their identification using SDS-polyacrylamide gel. We conclude that measurement of GST B1 or GST B2 in lung lavage fluid could be a useful aid in the diagnosis of lung malignancy.
Carcinogenesis 1990 Feb
PMID:Glutathione S-transferase isoenzymes in human bronchoalveolar lavage: a possible early marker for the detection of lung cancer. 230 56

The effects of 2-acetylaminofluorene (2-AFF) or sodium phenobarbital (PB) treatment subsequent to clofibrate (CF) administration in terms of preneoplastic lesion development and induction of hepatocellular carcinomas (HCC) were studied using Fischer 344 rats. Animals received CF (0.3% in diet) for the initial 30 weeks, and then either 2-AAF (0.01% in diet), PB (0.05% in diet) or basal diet until week 78. Further groups were initially given basal diet, and then treated with 2-AAF or PB week 30. Two-thirds partial hepatectomy was carried out on all animals at week 3, sacrifice of representative groups being performed at weeks 30, 48 and 78. No glutathione S-transferase placental form positive (GST-P+) or negative focal or nodular lesions were apparent at the cessation of CF administration. The induction of GST-P+ focal lesions by 2-AAF was markedly decreased at week 48 in the group previously given CF (P less than 0.05) and furthermore, the respective incidences of HCC at week 78 were 4/17 (23.5%) in the CF----2-AAF group and 7/17 (41.2%) in the 2-AAF alone case. No significant differences between CF----PB and PB alone groups were evident with regard to either GST-P+ lesions and HCC at weeks 48 and 78. No CF-specific GST-P negative neoplastic nodules or HCC were observed in any of the experimental groups. These results suggest that pretreatment with CF may inhibit the induction of GST-P+ focal lesions and HCC by subsequently administrated 2-AAF and that CF demonstrates no initiating activity for liver carcinogenesis under the present condition.
 ...
PMID:Modulatory interaction between initial clofibrate treatment and subsequent administration of 2-acetylaminofluorene or sodium phenobarbital on glutathione S-transferase positive lesion development. 230 5

The promoting potential of oxymetholone (OXM) administration on development of liver cell foci was investigated in male F344 rats previously treated with N-diethylnitrosamine (DEN). One week after a single injection of DEN (100 mg/kg, i.p.), rats were given OXM at a dietary level of 0.2% for the first 4 weeks and then at a concentration of 0.1% for an additional 35 weeks. All rats were killed at week 40 for histopathological and immunohistopathological examination of liver tissue. The numbers and areas of both clear cell and glutathione S-transferase placental form (GST-P) positive foci were significantly increased in the group treated with DEN and OXM as compared with the respective values for the DEN alone group. The results thus suggested that OXM possesses promoting potential for rat liver carcinogenesis.
 ...
PMID:Enhancing effect of oxymetholone, an anabolic steroid, on development of liver cell foci in rats initiated with N-diethylnitrosamine. 230 10

The effects of prolonged dietary administration of peroxisome proliferators, such as clofibrate, bezafibrate and di(2-ethylhexyl)phthalate (DEHP), on hepatic hydrogen peroxide (H2O2) level and on hepatic activities of the enzymes relating to H2O2 metabolism were examined. Male rats were treated for 79 weeks with the above three peroxisome proliferators. The activities of the peroxisomal beta-oxidation and catalase were increased 8- to 20-fold and 2- to 3-fold, respectively, after 2 or 4 weeks of treatment with these peroxisome proliferators. However at 79 weeks the peroxisomal beta-oxidation activity was 3-8 times that of control. The level of catalase activity was kept at approximately 2-fold even after prolonged treatment of peroxisome proliferators. Although the activities of glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST) were decreased 50-60% at 4-12 weeks by the treatment with peroxisome proliferators, from 20 to 79 weeks those activities approached control levels in the case of clofibrate and bezafibrate but not DEHP-fed rats; GSH-Px and GST activities were kept at approximately 40% those of control. However hepatic capacities of H2O2-degrading enzymes, catalase and GSH-Px, apparently exceeded the H2O2-generating levels obtained on the basis of peroxisomal beta-oxidation activities in the livers of control and treated rats throughout the experimental period. The hepatic H2O2 levels increased only slightly but this increase did not correspond to changes in peroxisomal beta-oxidation. Our results suggest that a large part of H2O2 produced by peroxisomal beta-oxidation could be rapidly scavenged by catalase and GSH-Px in the liver of rats treated with peroxisome proliferators.
Carcinogenesis 1990 Mar
PMID:Long-term effects of hypolipidemic peroxisome proliferator administration on hepatic hydrogen peroxide metabolism in rats. 231 Nov 88

Glutathione S-transferases play a central role in drug detoxification and have been implicated in the sensitivity of tumour cells to anticancer drugs. In this study, glutathione S-transferase (GST) isozyme expression in normal and tumour tissue from human lung, colon, stomach, breast, kidney and liver tissue has been quantified using sensitive and subunit specific radioimmunoassays (RIA), together with Western blot analysis and measurement of substrate metabolism. Glutathione S-transferase pi was the predominant GST in the majority of the tumours examined. The concentration of this enzyme was increased significantly in tumour tissue relative to normal lung, colon, and stomach tissue. A strong correlation was observed (r = 0.77, P less than 0.01) between GST activity and GST pi levels in those tumour samples. The concentrations of the alpha class GST, the predominant isoenzymes in normal stomach, kidney and liver, decreased dramatically in tumour tissue from these organs. Western blot analysis revealed the presence of novel polypeptides that cross-reacted with antisera raised against alpha and mu class GST. Our data demonstrates that although GST pi is the predominant GST isoenzyme in many tumours, significant levels of the other GST subunits are also present and collectively can represent a significant proportion of the GST content. Therefore the properties of all the GST isoenzymes need consideration when assessing the role of these proteins in drug resistance. Selenium-dependent glutathione peroxidase, an enzyme activity also implicated in the mode of action of certain antitumour agents, was also studied and shown to be the predominant glutathione-dependent peroxidase in all tumours except the hepatoma.
Carcinogenesis 1990 Mar
PMID:Glutathione S-transferase and glutathione peroxidase expression in normal and tumour human tissues. 231 Nov 89

The substituted 1,2-dithiole-3-thione oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione] protects against the acute and chronic toxicities of many xenobiotics, including aflatoxin B1, in rodents. These protective effects are mediated, in part, through elevation of glutathione S-transferase (GST) activities. Because studies by Coles et al. [Carcinogenesis (Lond.), 6: 693-697, 1985] suggested that the detoxication of aflatoxin through conjugation with glutathione is principally catalyzed by GST homodimer YaYa, we have investigated the regulation of the gene coding for the Ya subunit in the liver of F344 rats following dietary administration of oltipraz. Overall GST activity, as measured by conjugation with 1,2-dichloro-4-nitrobenzene or 1-chloro-2,4-dinitrobenzene, as well as the levels of GST Ya protein, was elevated 1.5-fold by 24 h and maximally (2.7- to 3.5-fold) and persistently after 5 days on a purified diet supplemented with 0.075% oltipraz. Steady state mRNA levels for GST subunit Ya, as quantified by slot blot analysis using rat liver GST complementary DNA clone pGTB38, were also elevated by 24 h, with a maximal elevation of 3-fold observed at 3 days. However, mRNA levels decreased thereafter, despite continued feeding of oltipraz. Northern blot analyses demonstrated that oltipraz did not alter the size of GST mRNA. Transcriptional activity of the GST Ya gene, as determined by nuclear run-off analysis, was increased 2-fold after 24-h feeding of oltipraz, was maximally induced 2.4-fold at 3 days, and returned to near control levels at 7 days, despite sustained feeding of oltipraz. Modulation of GST activity by oltipraz was not accompanied by changes in the methylation pattern at internal sites of the GST Ya gene. These results show that the initial induction of hepatic GST activity during oltipraz exposure correlates with changes in steady state levels of GST mRNA and rates of GST gene transcription; however, the continued elevation of GST enzymatic activities and GST Ya protein levels in the face of declining GST Ya mRNA levels and transcription rates suggests that additional mechanisms may be involved in regulating GST Ya expression by oltipraz.
 ...
PMID:Transcriptional control of glutathione S-transferase gene expression by the chemoprotective agent 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione (oltipraz) in rat liver. 231 12

A new approach to low-dose assessment of carcinogenic potential was applied to food contaminant pyrolysis products. Single intragastric doses of the carcinogenic pyrolysates, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) or 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline MeIQx), were given 12 h after two-thirds partial hepatectomy (PH) to F344 male rats. Two weeks thereafter the animals were placed on a basal diet containing 0.05% phenobarbital (PB) for 6 weeks combined with an i.p. administration of D-galactosamine (300 mg/kg) to facilitate growth of initiated cells. Both IQ and MeIQx clearly caused initiation of hepatocarcinogenesis as revealed by induction of preneoplastic placental-form glutathione-S-transferase-positive (GST-P+) hepatocyte foci composed of more than three cells (approximately 30 microns in diameter). A similar protocol without performance of PH before pyrolysate administration gave a positive result only for the IQ-treated group indicating that cell proliferation is essential during the low-dose, one-shot initiation step. IQ was found to be two to three times more potent in inducing GST-P+ foci using both protocols. The current approach could find application in practical carcinogenicity screening of chemicals, for which only small amounts are available.
Carcinogenesis 1990 Apr
PMID:Comparison of initiation potential of 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in an in vivo carcinogen bioassay system. 232 95

The effects of hepatocarcinogens (ethionine, thioacetamide, phenobarbital), non-hepatocarcinogens [N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)] and a hepatoinhibitor [(butylated hydroxyanisole (BHA)] were compared in medium- and long-term in vivo systems. In experiment I, 2 weeks after a single injection of diethylnitrosamine (DEN) groups of male F344 rats received chemical administration for 6 weeks, combined with partial hepatectomy at week 3 and were killed at the end of week 8. In experiment II, animals were treated in the same manner and then given basal diet and tap water (group 1) or chemical continuously (group 2) until the 2 year timepoint. Numbers and areas of glutathione S-transferase placental form (GST-P)-positive foci developing in the liver under medium-term bioassay conditions (experiment I) were found to closely correlate with eventual hepatocellular carcinoma incidences after continuation of test chemical administration (experiment II). Thus all of the hepatocarcinogens enhanced both the induction of GST-P-positive focal lesions and liver tumors. While non-hepatocarcinogens exerted no such effects, their influence being limited to inducing lesions in their own respective target organs such as urinary bladder cancers in the EHBN case and glandular stomach adenocarcinomas with MNNG, BHA demonstrated inhibition potential in both experiments. The observed correlation between long- and medium-term results strongly indicates the applicability of our medium-term bioassay system for detection of liver carcinogens.
Carcinogenesis 1990 Apr
PMID:Correlation between medium-term liver bioassay system data and results of long-term testing in rats. 232 97


<< Previous 1 2 3 4 5 6 7 8 9 10