Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The carcinogen 4-nitroquinoline 1-oxide (4-NQO) was found to rapidly deplete non-protein thiols (NPSH) from Ehrlich ascites tumor cells and V79 Chinese hamster fibroblasts. The effects of NPSH on 4-NQO metabolism were studied by measuring 4-hydroxyaminoquinoline 1-oxide formation, CN- -insensitive oxygen consumption, and reduction of ferricytochromes c + c1 in normal cells and in cells pretreated with the thiol reagent N-ethylmaleimide. Removal of thiols before treatment with 4-NQO resulted in increased production of 4-hydroxyaminoquinoline 1-oxide and increased production of nitro radicals. The NPSH thus appeared to play a significant role in 4-NQO detoxification. Glutathione, when present in culture medium during 4-NQO treatment, protected V79 cells from 4-NQO toxicity. Several mechanisms for reaction of 4-NQO with intracellular NPSH were indicated. Both V79 and Ehrlich cells contained appreciable amounts of glutathione S-transferase (EC 2.5.1.18), which catalyzes the nucleophilic substitution of the nitro group of 4-NQO with thiols. Greater thiol loss under oxic than under hypoxic conditions suggested oxidation by superoxide, peroxide, or hydroxyl radical formed in the course of 4-NQO reduction. In addition, reaction of thiols with nitro radicals or with nitrosoquinoline 1-oxide was indicated by the inhibitory effect of glutathione on oxygen consumption in solutions of 4-NQO and sodium ascorbate.
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PMID:Interactions of the carcinogen 4-nitroquinoline 1-oxide with the non-protein thiols of mammalian cells. 11 Apr 43

In vitro drug metabolism in the Hartley guinea pig was compared with that in two inbred guinea pig strains used as carriers for the line 10 hepatoma. We observed minor differences in enzyme specific activity among the three strains. Three weeks after intradermal inoculation of Strain 2 guinea pigs with line 10 hepatoma cells, cytochrome P450 levels and aminopyrine demethylase activity were significantly decreased. Seven to 10 days after inoculation with the ascites form of the tumor, the activities of aniline and biphenyl hydroxylases, p-aminobenzoic acid N-acetyltransferase, and dichloronitrobenzene glutathione S-aryltransferase, in addition to those of cytochrome P450 and aminopyrine N-demethylase, were probably also described.
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PMID:Effect of strain differences and tumor presence on microsomal drug metabolism in the guinea pig: brief communication. 20 Jul 61

The oncosuppressive effect of melatonin on 9,10-dimethyl-1,2-benzanthracene (DMBA) induced rat mammary tumorigenesis led us to assess its possible modulatory influence on representative hepatic and mammary drug metabolizing enzymes in DMBA treated female Holtzman rats, reared in short and long photoperiods. Melatonin treated rats in either photoperiod showed a significant induction in hepatic and mammary levels of glutathione (GSH) and cytosolic activities of glutathione S-transferase (GST) when compared with the corresponding controls, along with a significant drop in hepatic microsomal contents of cytochromes b5 and P450. This induction of GSH and GST, and depletion of cytochromes b5 and P450 by melatonin may possibly be related to its anticarcinogenic potential in this tumor model.
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PMID:A possible modulatory influence of melatonin on representative phase I and II drug metabolizing enzymes in 9,10-dimethyl-1,2-benzanthracene induced rat mammary tumorigenesis. 128 33

The detection of preneoplastic cells is very important for the analysis of carcinogenic processes and for developing strategies for prevention and treatment of cancer. We have been investigating enzyme alterations occurring during rat chemical hepatocarcinogenesis, especially to find more specific enzyme markers for preneoplastic hepatic lesions. We identified the placental form of glutathione S-transferase (GST-P; GST 7-7) as a new marker enzyme for preneoplastic hepatocytes. We also found human placental form, GST-pi, to be a possible tumor marker for various human tissues except liver. In this article, their properties and possible functions are reviewed on basis of our recent investigations. A peroxisomal enzyme, enoyl CoA hydratase, in also described as a possible negative marker for rat preneoplastic hepatic foci/nodules and hepatomas induced by peroxisome proliferators.
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PMID:Specific expression of glutathione S-transferase Pi forms in (pre)neoplastic tissues: their properties and functions. 130 37

The mRNA levels of three phosphoseryl/phosphothreonyl protein phosphatases, PP1, PP2A and PP2C, in rat liver have been determined by Northern blot analysis in various stages of rat chemical hepatocarcinogenesis using a Solt-Farber model. Five weeks after administration of diethylnitrosamine, the mRNA levels of PP1 alpha, PP2A and PP2C were elevated 8, 29 and 11 times, respectively, as compared to those of the control livers. However, in primary hepatoma induced according to the Solt-Farber model, the mRNA levels of all three protein phosphatases were dramatically decreased to normal levels or even to much lower levels, whereas the mRNA level of glutathione S-transferase placental form, a tumor marker protein, was greatly elevated as compared with that of the control livers. In a poorly differentiated hepatoma AH13, a line of rat ascites hepatoma, the mRNA level of PP1 alpha was 5.6 times higher than that of the control livers, whereas the mRNA lever of PP2C was almost the same as that of the control livers and the level of PP2A mRNA was distinctly lower than that of the control livers. These data appear to suggest some involvement of protein phosphatases in hepatocarcinogenesis.
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PMID:mRNA levels of catalytic subunits of protein phosphatases 1, 2A, and 2C in hepatocarcinogenesis. 131 79

To study the factors contributing to tumor sensitivity to adriamycin (ADR) in vivo, the relationship between mRNA expression of the MDR1, GST-pi and topoisomerase II genes and tumor response to ADR was examined in six human xenograft tumors derived from two esophageal, two gastric and two colon cancers. A significant tumor response to ADR was observed in two esophageal xenograft tumors of six tumor lines, and one gastric tumor partially responded to ADR. mRNA expression of the MDR1 and GST-pi genes was elevated in five tumor lines including three ADR responsive tumors, whereas mRNA expression of the topoisomerase II gene was detected in all six tested tumor lines. Topoisomerase II mRNA expression levels in ADR responsive tumors were higher compared with those of ADR unresponsive tumors. No significant relationship between mRNA expression of the MDR1 and GST-pi genes and ADR sensitivity was found. In contrast, topoisomerase II mRNA expression was significantly correlated with tumor sensitivity to ADR (p less than 0.01). Moreover, topoisomerase II mRNA expression was significantly correlated with the growth fraction (S-phase fraction) in the cell cycle kinetics (p less than 0.01). These results indicate that topoisomerase II mRNA expression in association with the high growth fraction may be an important in vivo factor to contribute to ADR sensitivity in human tumors.
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PMID:Factors contributing to adriamycin sensitivity in human xenograft tumors: the relationship between expression of the MDR1, GST-pi and topoisomerase II genes and tumor sensitivity to adriamycin. 131 32

Glutathione S-transferases are involved in the detoxification of carcinogens and xenobiotics and are potentially associated with the development of drug-resistance. Forty-six testicular germ cell tumors and 33 adjacent normal testicular tissue specimens were analyzed at the RNA level for the expression of glutathione S-transferase alpha and pi. Glutathione S-transferase alpha was expressed in 31 of the 33 normal testicular tissues (94%) but in only three of the 46 germ cell tumors (7%). Glutathione S-transferase pi mRNA was detected in all normal and malignant testicular tissue samples. Thirteen testicular germ cell tumors and eight normal testicular tissue samples were analyzed at the protein level. The mean specific activity of total cytosolic glutathione S-transferase in tumor tissue was decreased by about 80% as compared to normal testicular tissue. Protein analysis of the glutathione S-transferase subunits of normal testicular tissue demonstrated the presence of the glutathione S-transferase classes alpha, mu and pi, with a predominance of the mu class. In testicular germ cell tumors the glutathione S-transferase subunit pattern showed a predominance of glutathione S-transferase pi representing 88% +/- 3% of total glutathione S-transferase. Since all three glutathione S-transferase isoenzyme classes contribute to the resistance to antineoplastic drugs, the altered glutathione S-transferase isoenzyme pattern and the decrease of glutathione S-transferase activity may play a role in the high inherent drug sensitivity of human testicular germ cell tumors.
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PMID:Glutathione S-transferases in human testicular germ cell tumors: changes of expression and activity. 131 14

A mu class glutathione S-transferase gene (hGSTYBX) is expressed in the DDT1MF-2 hamster smooth muscle tumor cell line. This gene is glucocorticoid responsive, and near maximal induction was found to occur within 24 h. The induced mRNA was very stable with a half-life of more than 48 h. Serum had no effect on either constitutive or glucocorticoid induced hGSTYBX expression. Although dibutyryl cAMP, phenobarbital, and 12-O-tetradecanoylphorbol-13-acetate did not alter hGSTYBX expression, testosterone and retinoic acid were each able to increase hGSTYBX expression in a concentration dependent manner. These results demonstrate a unique pattern of responsiveness of the hamster gene compared to the glutathione S-transferase genes of other species.
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PMID:Glucocorticoid, androgen, and retinoic acid regulation of glutathione S-transferase gene expression in hamster smooth muscle tumor cells. 131 23

Dehydroepiandrosterone, a major secretory steroid hormone of the human adrenal gland, possesses mitoinhibitory and anticarcinogenic properties. It also induces peroxisome proliferation in the livers of rats and mice. Because peroxisome proliferators exhibit hepatocarcinogenic potential, it is necessary to examine the long term hepatic effects of dehydroepiandrosterone since this hormone is contemplated for use as a potential cancer chemopreventive agent in humans. Dehydroepiandrosterone was administered in the diet at a concentration of 0.45% to F-344 rats for up to 84 weeks. At the termination of the experiment, 14 of 16 rats developed hepatocellular carcinomas. Liver tumors induced by dehydroepiandrosterone lacked gamma-glutamyl transpeptidase and glutathione S-transferase (placental form); these phenotypic properties are identical to the features exhibited by liver tumors induced by other peroxisome proliferators. Dehydroepiandrosterone was also shown to markedly inhibit liver cell [3H]thymidine labeling indices, suggesting that cell proliferation is not a critical feature in liver tumor development with this agent. These results show that although dehydroepiandrosterone exerts anticarcinogenic effects in a variety of tissues, the peroxisome-proliferative property makes it a hepatocarcinogen.
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PMID:Hepatocarcinogenicity of dehydroepiandrosterone in the rat. 131 32

The expression of cytosolic glutathione S-transferase (GST) isoenzymes has been assessed in a series of 74 primary human breast carcinomas using an immunohistochemical method. GST pi was detected in sections from all 74 tumours; it was expressed by non-epithelial (stromal and inflammatory) cells in 62 tumours (84 per cent), but by tumour epithelium in only 35 (47 per cent). Non-neoplastic mammary epithelium was uniformly positive for GST pi. Expression of GST alpha and mu was observed in 19 and 42 per cent of the tumours, respectively, and was largely confined to the neoplastic component. Lack of staining of tumour epithelium for GST pi was significantly associated with poorer tumour differentiation (higher grade). There was no association between expression of any of the three isoenzymes and either menopausal status or expression of c-erbB-2 oncogene protein product. Immunohistochemistry is a useful method for the investigation of expression and cellular localization of GSTs within tumours; such data are needed to improve our understanding of the role of these enzymes in neoplasia and in resistance to cytotoxic drug therapy.
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PMID:Immunohistochemical demonstration of glutathione S-transferases in primary human breast carcinomas. 134 80


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