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)

The effect of voluntary exercise on azoxymethane-induced hepatocarcinogenesis was investigated in male F344 rats. Beginning at 5 weeks of age, all animals were divided into two groups (sedentary and exercise) and fed AIN-76A semipurified diet ad libitum. At 7 weeks of age, animals were given azoxymethane (AOM) s.c. at a dose level of 15 mg/kg of body weight, once weekly for 2 weeks. Four days after the second dose of AOM, all animals in the exercise group were housed in individual wheel-cage units and the animals in the sedentary group were housed in plastic cages. The experiment was terminated at 38 weeks post-AOM treatment. Body weights of animals in the exercise and sedentary groups were comparable. Immunohistochemical staining of glutathione S-transferase placental form (GST-P) was performed in the liver and measured GST-P positive foci. Density (number of GST-P positive foci/cm2 area of liver section), average area of foci and unit area of foci were significantly inhibited in the exercise group, although the incidence of neoplastic nodules and GST-P positive foci were unaffected by the exercise. Thus, energy expenditure due to exercise may reduce hepatocarcinogenesis in a laboratory animal model.
Cancer Lett 1992 Mar 31
PMID:Effect of voluntary exercise on azoxymethane-induced hepatocarcinogenesis in male F344 rats. 155 8

Many furan-containing natural products that induce increased activity of the glutathione S-transferase (GST) enzyme system have been found to inhibit tumorigenesis in laboratory animals. 2-n-Heptylfuran (HF) and 2-n-butylthiophene (BT), a sulfur analogue of furan, are two of the many furans and thiophenes formed during the roasting process of meat. BT and HF, when administered by gavage at doses that ranged from 11 to 90 mumol, induced increased GST activity in various tissues of A/J mice. At 90 mumol/dose, BT induced increased GST in the liver, small bowel mucosa, and lung. No increase in enzyme activity was found in the forestomach. HF was an enzyme inducer in the liver, small bowel mucosa, and forestomach but was inactive in the lung. The acid-soluble sulfhydryl level, a good measure of glutathione contents in tissues, was examined in tissue homogenates from mice treated with BT and HF. BT induced significant increase of GSH in the liver and lung at the higher doses. No change was observed in either the small bowel mucosa or the forestomach. A 50-mumol dose of HF was found to increase GSH level in all four tissues studied. The inhibition of lung and forestomach tumorigenesis was carried out with A/J mice using benzo[a]pyrene as the carcinogen. BT treatment resulted in a reduction of tumor multiplicity in the lung and forestomach. The tumor incidence in the forestomach was reduced significantly. The potency of HF as inhibitor of carcinogenesis was similar to that of BT in the forestomach of mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Nutr Cancer 1992
PMID:Inhibitory effects of 2-n-heptylfuran and 2-n-butylthiophene on benzo[a]pyrene-induced lung and forestomach tumorigenesis in A/J mice. 157 41

The anticarcinogenic effect of dietary turmeric on benzo[a]pyrene-(BP) induced forestomach neoplasia and 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin tumorigenesis in female Swiss mice was evaluated. To further elucidate the mechanism of antineoplastic action of turmeric, its effect on the hepatic cytochrome b5, cytochrome P-450, glutathione, and glutathione S-transferase activities was studied in female Swiss mice. Turmeric (2% or 5%) in the diet significantly inhibited the BP-induced forestomach tumors, and this response was dose and time dependent. The 2% turmeric diet significantly suppressed DMBA-induced skin tumors in mice. The 5% turmeric diet for seven consecutive days resulted in a 38% decrease in the hepatic cytochrome b5 and cytochrome P-450 levels. Glutathione content was increased by 12%, and the glutathione S-transferase activity was enhanced by 32% in the liver. Our results document a protective effect of turmeric on BP-induced forestomach and DMBA-induced skin tumors in mice.
Nutr Cancer 1992
PMID:Chemopreventive effect of turmeric against stomach and skin tumors induced by chemical carcinogens in Swiss mice. 157 46

The expression of glutathione transferase pi (GST pi) was studied in leukemic cells from 60 patients with acute nonlymphoblastic leukemia at diagnosis and at progressing stages of the disease. A polyclonal rabbit antibody to human placental GST pi coupled with peroxidase antiperoxidase staining was used for immunodetection of GST pi on sections of routinely fixed bone marrow clots. All patients had received induction therapy based on an anthracycline and a standard dose of ara-C. The expression of GST pi at diagnosis was significantly correlated with response to induction therapy, duration of first remission, and overall survival. Twenty-nine of 36 samples of bone marrow from patients that entered complete remission (CR) following primary induction therapy showed a low expression, whereas nine of 16 sections from patients with resistant disease showed a high expression of GST pi (P less than or equal to 0.03). Of 40 sections that showed a low expression of GST pi, 29 (73%) were taken from patients that achieved a CR, whereas 12 of 19 sections that showed a high expression of the enzyme were from patients with resistant disease or that entered CR only after additional therapy (P less than or equal to 0.02). The median duration of first CR was 18.2 mo for patients whose cells showed a low expression of GST pi compared with 6.7 mo for those that entered CR in spite of a high expression of the enzyme (P less than or equal to 0.005). Of cells from ten patients that at the time of study were in a continuous first CR, none expressed high concentrations of GST pi. The expression of GST pi remained rather constant in most patients as the disease progressed to clinical resistance. At relapse there was no significant correlation between the expression of GST pi and treatment results but, of ten patients that entered a second CR or achieved a partial remission, only one showed a high expression of the enzyme. We conclude that there was a significant correlation between the expression of GST pi at the time of diagnosis and the subsequent treatment results and that GST pi is a useful marker for clinical resistance to cytostatic drugs in acute nonlymphoblastic leukemia.
Cancer Res 1992 Jun 15
PMID:Expression of glutathione transferase pi as a predictor for treatment results at different stages of acute nonlymphoblastic leukemia. 159 86

Following the oral feeding of a polyphenolic fraction isolated from green tea (GTP) in drinking water, an increase in the activities of antioxidant and phase II enzymes in skin, small bowel, liver, and lung of female SKH-1 hairless mice was observed. GTP feeding (0.2%, w/v) to mice for 30 days significantly increased the activities of glutathione peroxidase, catalase, and quinone reductase in small bowel, liver, and lungs, and glutathione S-transferase in small bowel and liver. GTP feeding to mice also resulted in considerable enhancement of glutathione reductase activity in liver. In general, the increase in antioxidant and phase II enzyme activities was more pronounced in lung and small bowel as compared to liver and skin. The significance of these results can be implicated in relation to the cancer chemopreventive effects of GTP against the induction of tumors in various target organs.
Cancer Res 1992 Jul 15
PMID:Enhancement of antioxidant and phase II enzymes by oral feeding of green tea polyphenols in drinking water to SKH-1 hairless mice: possible role in cancer chemoprevention. 161 81

Potential synergism between 4 antioxidants acting at low doses on development of glutathione S-transferase placental form (GST-P)-positive liver cell foci was examined in male rats initially given diethylnitrosamine (200 mg/kg, i.p.). Beginning 2 weeks after the initiation, rats received the antioxidants, individually or in combination, in the diet for 6 weeks. All rats were subjected to two-thirds partial hepatectomy at week 3 and killed at week 8. The numbers and areas of GST-P-positive foci were significantly decreased by single treatment with butylated hydroxyanisole (BHA, 1%), tert-butylhydroquinone (TBHQ, 1%) and catechol (0.8%), but not with sesamol (0.5%). Combined treatments (BHA + TBHQ, catechol + sesamol, or all 4 chemicals) at a quarter of the above dose levels resulted in decrease in numbers and areas of foci to levels less than the sums of individual inhibition data obtained with the one-quarter levels. Although these combined effects were not statistically significant in the additive model, the results indicate possible synergistic suppression of carcinogenesis by low-dose combined treatment with anti-cancer agents and the usefulness of the present protocol for this type of analysis.
Jpn J Cancer Res 1992 May
PMID:Suppression of diethylnitrosamine-initiated preneoplastic foci development in the rat liver by combined administration of four antioxidants at low doses. 161 95

Certain waterblooms of toxic cyanobacteria (blue-green algae) are a health threat because of their production of toxic peptides, termed microcystins, which cause liver damage in wild and domesticated animals. The most widely studied microcystin is microcystin-LR, a heptapeptide containing the two L-amino acids, leucine and arginine. The inhibition of protein phosphatase type 1 and type 2A activities by microcystin-LR is similar to that of the known protein phosphatase inhibitor and tumor promoter okadaic acid. We show in this report that microcystin-LR, applied below the acute toxicity level, dose-dependently increases the number and percentage area of positive foci for the placental form of glutathione S-transferase in rat liver, which was initiated with diethylnitrosamine. The result was obtained independently through two animal experiments. This observation indicates that microcystin-LR is a new liver tumor promoter mediated through inhibition of protein phosphatase type 1 and type 2A activities. This provides further evidence that the okadaic acid pathway is a general mechanism of tumor promotion in various organs, such as mouse skin, rat glandular stomach and rat liver.
J Cancer Res Clin Oncol 1992
PMID:Liver tumor promotion by the cyanobacterial cyclic peptide toxin microcystin-LR. 161 89

We have established cis-diamminedichloroplatinum(II) (cisplatin) resistant human small cell lung cancer cell lines, H69/CDDP0.2 and H69/CDDP, to investigate the mechanism of acquired resistance to cisplatin. H69/CDDP0.2 and H69/CDDP were 6- and 11-fold resistant to cisplatin compared with the H69 parental cell line. H69/CDDP was also resistant to cadmium chloride (2-fold), cis-diammine(glycolato)platinum (4-fold), 4-hydroperoxycyclophosphamide (3-fold) and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosour ea (4-fold) if the drug concentrations that inhibit cell growth by 50% from growth inhibition assay were compared. There was no significant difference in the cisplatin accumulation among these cell lines. Although DNA interstrand cross-link formations, determined by filter elution assay in H69/CDDP0.2 and H69/CDDP, was decreased to 20 to 30% of that in H69 parental cells, the repair capacity of DNA interstrand cross-links was equivalent in all three cell lines. Intracellular glutathione content was equal in all cell lines. H69/CDDP had the highest glutathione S-transferase activity (H69, 11 nmol/min/mg protein, H69/CDDP0.2, 12 nmol/min/mg protein; H69/CDDP, 74 nmol/min/mg protein, respectively) and an overexpression of glutathione S-transferase pi mRNA. The drug concentrations that inhibit cell growth by 50% for cisplatin in all cell lines were decreased by treatment with ethacrynic acid, an inhibitor of glutathione S-transferase pi, but this did not alter the relative degree of resistance. Intracellular metallothionein content (H69, 14 pmol/mg protein, H69/CDDP0.2, 22 pmol/mg protein; H69/CDDP, 33 pmol/mg protein, respectively) and expression of metallothionein mRNA were correlated with the drug concentrations that inhibit cell growth by 50% of the three cell lines for cisplatin and cadmium chloride. The present study suggested the importance of metallothionein in the mechanisms of cisplatin resistance.
Cancer Res 1991 Jun 15
PMID:Metallothionein content correlates with the sensitivity of human small cell lung cancer cell lines to cisplatin. 164 16

GST-pi has been known to be markedly increased in human (pre) neoplasms of several organs. In this paper, the significance of immunohistochemical detection of GST-pi in human malignant tumors of the skin was studied. In specimens from 40 patients with various skin cancers, malignant melanoma, Paget's disease and undifferentiated squamous cell carcinoma showed strong reactivity in GST-pi staining. The reactions were negative or weak in Bowen's disease, basal cell epithelioma and solar keratosis. In normal melanocytes, eccrine, apocrine, and breast gland cells stained positively but not in keratinocytes, sebaceus gland and fibroblasts. While immunohistochemical detection of GST-pi in the skin was not specific for malignancies, it contributed to aid the distinction of squamous cell carcinoma from other keratinocytic tumors. GST-pi might provide potentially useful information on chemosensitivity of skin cancer, and might serve as a biomarker of disease activity.
 ...
PMID:Expression of glutathione S-transferase-pi in malignant skin tumors. 164 97

The absence of estrogen receptors (ER) in human breast tumors has been associated with a poorer prognosis compared to patients with ER positive breast cancer. Previous studies from our laboratory have shown that a multidrug resistant human breast cancer cell line selected for resistance to Adriamycin (ADR) exhibited markedly increased expression of both the pi class glutathione S-transferase (GST-pi) and the selenium-dependent glutathione peroxidase. These studies also revealed that the ER status was inversely related to the expression of GST-pi in six human breast cancer cell lines and primary tumor specimens. In the present study, we have examined the relationship between ER status and several biological properties of these cells, including their levels of glutathione peroxidase (GSH-Px) and catalase expression, their capacity to generate toxic hydroxyl radicals (degrees OH) by redox cycling of ADR, and their sensitivities to the cytotoxic effects of ADR and the oxidant, H2O2. Our results show that expression of GSH-Px, but not catalase, is inversely related to the ER status in these cell lines. Formation of the degree OH induced by treatment of cells with ADR was inversely proportional to the GSH-Px activity in these cell lines, and thus directly related to the ER status. Sensitivity of these cells to ADR or to H2O2, however, was not consistently related to ER status, GSH-Px, or catalase activity, or to ADR induced degree OH radical formation. These results indicate that these parameters are not predictive of cellular susceptibility to oxidative damage in these cell lines under the conditions studied.
Cancer Commun 1991 Aug
PMID:Selenium-dependent glutathione peroxidase expression is inversely related to estrogen receptor content of human breast cancer cells. 165 87


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