Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study investigated the influence of selenium intake, over 8 weeks, on vitamin A level and on enzymatic antioxidant defence in the liver of young rats. Deficient animals were fed a well-balanced diet but without selenite addition; the Se content of this diet which originated from natural Se content of ingredients was 0.05 mg/kg. Controls were fed the same diet with 0.40 mg/kg added Se. The two other groups received high levels of Se, 2.05 or 4.05 mg/kg. Excessive Se intake decreased the concentrations of retinol and retinyl palmitate in the liver. The linear regression analysis indicated a significant (P < 0.001) dose-dependent vitamin A decline. As expected, Se deficit lowered glutathione peroxidase activity. The highest Se excess decreased the enzymatic antioxidation: Zn,Cu superoxide dismutase, catalase, glutathione peroxidase activities. Data showed that high dietary Se can sometimes enhance carcinogenesis and our results suggest that it is best to be cautious in administrating Se to humans with the aim of preventing diseases.
 ...
PMID:Excessive dietary selenium decreases the vitamin A storage and the enzymatic antioxidant defence in the liver of rats. 828 96

Gastroscopy with gastric biopsy was performed in 109 individuals aged 25-71 years. Activities of three antioxidant enzymes were assayed in biopsy specimens: Cu/Zn superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Patients were classified according to the endoscopic and histological findings in the following groups: normal findings (N), superficial gastritis (SG), mild (MAG) and severe (SAG) atrophic gastritis, gastritis after partial gastrectomy (PGG), hyperplastic polyp (HP), and gastric adenoma (A). Compared with the N group, increased activity of SOD was found in groups SG (+37%), PGG (+67%) and A (+35%), increased CAT activity in PGG (+40%), and increased GSH-Px activity in groups SG (+57%), SAG (+46%), PGG (+185%), HP (+50%) and A (+50%). Increased activity of antioxidant enzymes could be induced by higher concentrations of superoxide anion radicals, hydrogen peroxide and lipid peroxides, produced by phagocytic leucocytes or by polyunsaturated fatty acid in cellular membranes of gastric mucosa. The relation of reactive oxygen species to the induction of precancerous conditions and to carcinogenesis of the stomach requires further study.
 ...
PMID:Increased mucosal antioxidant enzyme activities in chronic gastritis and benign gastric polyps. 828 10

Recently El-Bayoumy and coworkers have reported that 1,4-phenylene-bis(methylene)selenocyanate (p-XSC) was very effective in inhibiting 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis and adduct formation during the initiation phase (Cancer Res., 52, 2402-2407, 1992). Furthermore, this compound was found to be well tolerated by rats at high doses. The present study was designed to extend these earlier observations by investigating the response to lower levels of p-XSC given either before or after DMBA administration. At a level of 15 p.p.m. Se, p-XSC suppressed total mammary tumor yield by 80% and 52% in the initiation phase and post-initiation phase, respectively. A dose-response effect was evident in the range 5-15 p.p.m. Se. When p-XSC was given at a level of 5 p.p.m. Se during the entire course of the experimental period, total tumor yield was reduced by half. This dose is about 4 x less than the maximum tolerable dose (MTD). Other selenocyanate analogs were also examined in an attempt to obtain information on their respective chemopreventive index, which is calculated as the ratio of MTD to the effective dose which produces approximately a 50% inhibition in total tumor yield (ED50). The reagents studied included potassium selenocyanate, methyl selenocyanate and benzyl selenocyanate, as well as sodium selenite (reference compound). Compared to p-XSC, which has a chemopreventive index of 4.0, the other four compounds have a lower index ranging from 1.3 for sodium selenite and potassium selenocyanate to 2.0 for methyl selenocyanate and 2.5 for benzyl selenocyanate. A high chemopreventive index signifies that a compound is well tolerated at doses required for cancer suppression. The last component of the present study involved the repletion assay of liver glutathione peroxidase in selenium-deficient rats as a biomarker to estimate the metabolizability of the above selenium compounds. The bioavailability data suggest that the selenium from p-XSC is not as efficiently incorporated into glutathione peroxidase as the selenium from selenite or the other selenocyanate analogs. Currently, we are working under the hypothesis that the chemical structure of the RSeCN compound could affect activity per se and also influence the rate of release of selenium from the parent compound, thereby impacting on the anticarcinogenic efficacy, tolerance and bioavailability of the compound.
Carcinogenesis 1994 Feb
PMID:Comparative effect of inorganic and organic selenocyanate derivatives in mammary cancer chemoprevention. 831 7

The activities of several enzymes involved in the antioxidant system of the cell were studied in parallel to cytogenetic alterations at various times after SV40 infection and transformation of human fibroblasts. At early passages after SV40 infection, glutathione reductase (GSR), glutathione peroxidase (GPX), glutathione transferase (GST) and glucose-6-phosphate dehydrogenase (G6PD) activities were decreased. This, associated with the low superoxide dismutase (SOD) and catalase activities previously noticed in these cells, suggested that they are in a highly pro-oxidant status. Although chromosomes carrying the genes encoding these enzymes are frequently underrepresented, there is no direct relationship between the number of chromosomes and enzyme activities. Except for GPX, all the activities tend to increase in established cell lines reaching levels comparable to those of non-transformed fibroblasts. The late increase of G6PD activity may correlate with the frequent duplication of the early replicating X. GSR seems to correlate with G6PD activity and GPX to SOD total activity. The most striking alterations affect mitochondrial and peroxisomal enzymes activities: SOD, GPX and catalase.
Carcinogenesis 1993 Jan
PMID:Alterations of the glutathione cycle enzymes during and after SV40-transformation of human fibroblasts. 838 Oct 54

A 58 kDa selenium-labeled protein purified from mouse mammary epithelial cells (MMEC) was used to examine whether selenium modulates protein synthesis or is just a marker for cellular selenium status. The protein was isolated using Sephadex G150 gel filtration and DEAE-Sephadex A50 ion-exchange chromatography. It was further analysed using 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and was found as a single spot with a pI of 4.6. The immunoreactivity with anti-58 kDa antiserum and the 75Se signal co-localized on a single 58 kDa protein band on both 1D- and 2D-PAGE. Partial amino acid analysis of the peptide showed homology with the thiol protein disulfide oxidoreductase (TPDO). Varying the selenium concentration in culture medium did not affect the protein content or the immunoreactivity of the 58 kDa protein. Additionally, selenium did not seem to regulate the activity of TPDO in TM6 cells. The glutathione peroxidase activity of TM6 cells, taken as the internal positive control, was enhanced with the increase in selenium concentration in the medium. The results suggest that selenium is attached to the 58 kDa protein, but does not regulate either its protein synthesis or its functional activity. We conclude that selenium labeling of the 58 kDa protein reflects the cellular selenium status but probably is not involved in its chemopreventive ability.
Carcinogenesis 1993 Sep
PMID:Significance of selenium-labeled proteins for selenium's chemopreventive functions. 840 16

Fenofibrate, the hypolipidemic drug and peroxisome proliferator, was given to mice (0.23% w/w in the diet) during 1-3 weeks and enzyme activities, H2O2 concentration, and H2O2 production rate were determined. A maximal increase of 150% in liver/body weight ratio was observed after 3 weeks of treatment. Acyl-CoA oxidase, catalase and uricase activities were increased by 712%, 506% and 41% respectively by treatment with fenofibrate. Se- and non Se-glutathione peroxidase and Mn-superoxide dismutase activities were increased by 331%, 188% and 130% respectively in the liver of 2 weeks-treated mice. Cu-Zn superoxide dismutase activity was not affected by fenofibrate treatment. H2O2 steady-state concentration showed an increase of 89% after 2 weeks of treatment. H2O2 production rates, and the steady-state concentrations of the intermediates HO, R and ROO, calculated using experimental data, were higher in the liver of fenofibrate-treated mice than in control animals. According to our findings, the imbalance between H2O2 production and its degradation by its metabolizing enzymes during peroxisome proliferation, would result in an increased level of H2O2 steady-state concentration, with the resulting oxidative stress which may lead to the generation of oxidative damage and to the induction of liver carcinogenesis.
 ...
PMID:Hydrogen peroxide metabolism during peroxisome proliferation by fenofibrate. 854 49

Most colon carcinomas are preceded by an adenomatous polyp--adenoma-carcinoma sequence. Active oxygen species (AOS) can play a role in the pathogenesis of this process. Antioxidant enzymes (AE) are the primary defense against the deleterious effect of AOS. Activities of AE in 56 individuals with colorectal adenoma (CA), 29 individuals with colorectal carcinoma (CC) and in 24 control subjects were examined. Biopsy specimens from the non-neoplastic colonic mucosa and from the CA and CC were taken during colonoscopy for histological and enzymological analysis. Activities of following AE were estimated: CuZn-superoxide dismutase (CuZn-SOD), catalase (CAT) and glutathione peroxidase (GPx). It was found that individuals with CA and CC were characterized by: (1) increased activities of CAT and GPx in non-neoplastic mucosa, that persisted in some of the patients even after removal of tumors; (2) increased activities of CuZn-SOD, CAT and PGx in CA and CC tissues. It can be inferred that the accumulation of peroxides in the non-neoplastic colonic mucosa induced higher activities of CAT and GPx. The reasons of high activities of all AE in the tissues of CA and CC and their relation to carcinogenesis are not clear and require further studies.
 ...
PMID:Increased antioxidant enzyme activities in the colorectal adenoma and carcinoma. 855 7

To study the genetic changes that generate resistance to oxidants in mammalian cells, we isolated cell lines that are resistant to the naphthoquinone, menadione, from a Chinese hamster ovary cell line (CHO-K1). Corss-resistance to other oxidants (H2O2 and sodium arsenite) was observed. The IC50 of menadione (measured using a clonogenic assay) was 7.8-fold greater for one menadione-resistant cell line (MRc40) than for CHO-K1. Acquisition of resistance was associated with elevations of 2- and 3.2-fold in the low molecular weight thiols, glutathione and cysteine, respectively. Further, characterization demonstrated significant changes in the expression of enzymes associated with the oxidative stress response and with protection against oxidizing agents. The expressions of glutathione S-transferase pi (GST pi), glutathione peroxidase (GPX) and heme oxygenase mRNAs were all increased. Accompanying these changes the enzyme activity of GST pi, GPX and gamma-glutamyl transpeptidase (gamma-GT) were also elevated. Interestingly, in a revertant cell line heme oxygenase overexpression approached wild-type levels. Intriguingly, similar changes in gene expression seen in the menadione-resistant cells were also observed in wild-type cells following transient oxidative stress, indicating that the observed changes in the resistant line may be due to the immortalization of a normally transient adaptive stress response.
Carcinogenesis 1996 Apr
PMID:Relationship between the adaptive response to oxidants and stable menadione-resistance in Chinese hamster ovary cell lines. 862 73

There is much evidence suggesting a possible role of reactive oxygen-derived substances in the pathogenesis of both ulcerative colitis and colon cancer. The antioxidant effects of 5-aminosalicylic acid (the active moiety of olsalazine) on induction of colon cancer in an experimental model using 1,2-dimethylhydrazine were studied in male Wistar rats. The levels of reduced glutathione were significantly (P < 0.01) decreased (by approximately 50%) in neoplastic tissues of rats receiving 1,2-dimethylhydrazine alone and olsalazine treatment significantly (P < 0.01) reduced the extent of this alteration. Adjacent tissues from rats receiving either carcinogen alone or carcinogen and olsalazine showed comparable levels of glutathione and these were significantly (P < 0.01) lower than corresponding control values and higher than corresponding values from neoplastic tissues. Activity of the glutathione regenerating enzyme glutathione reductase was significantly (P < 0.01) decreased (by approximately 40%) in neoplastic colonic tissue and this alteration was unaffected by olsalazine treatment. Neither carcinogen nor olsalazine treatment caused alterations in activity of glutathione reductase in adjacent tissue as compared with corresponding control values. Activity of the glutathione utilizing enzyme glutathione peroxidase was significantly (P < 0.01) increased (almost doubled) in neoplastic tissue of rats treated with carcinogen alone. Olsalazine treatment significantly (P < 0.01) reduced the elevation in glutathione peroxidase activity in neoplastic tissues of rats treated with the carcinogen. Glutathione peroxidase showed comparable activity in adjacent tissue from rats treated with either carcinogen alone or a combination of carcinogen and olsalazine and these values were significantly (P < 0.01) lower than corresponding control values. Colonic neoplastic tissues from all experimental groups of animals showed a small, but statistically significant (P < 0.05), decrease in superoxide dismutase activity compared with that in corresponding tissues from control animals.
Carcinogenesis 1996 May
PMID:Endogenous antioxidant status in neoplastic and adjacent tissues in 1,2-dimethylhydrazine-induced colon cancer in rats: effects of olsalazine. 864 Sep 47

Four anticarcinogens (oltipraz, alpha-tocopherol, beta-carotene and phenethylisothiocyanate [PEITC]) were studied with respect to their effects on oesophageal, gastric, colonic and hepatic (i) glutathione (GSH) content, (ii) glutathione S-transferase (GST) enzyme activity, (iii) GST isoenzyme levels, and (iv) glutathione peroxidase (GPx) enzyme activity in male Wistar rats. GST enzyme activity was significantly increased in oesophagus (1.9X) and colon (1.2X) by PEITC and in liver (1.4X) by oltipraz. GST Alpha was doubled in the liver by oltipraz, alpha-tocopherol and PEITC. GST Mu levels were increased by beta-carotene and PEITC in stomach and liver, by oltipraz in liver and by alpha-tocopherol in stomach. PEITC induced colonic GST Pi levels (1.3X). GSH content was induced in liver by oltipraz (1.4X) and alpha-tocopherol (1.2X) and in colon by PEITC (1.6X). Each of the anticarcinogens tested increased GPx activity at one or more sites: Se-dependent and total GPx activities were induced in 31.3% and 37.5% of all possibilities, respectively. Major induction in total GPx was found in stomach by alpha-tocopherol (1.8X). In conclusion our data demonstrate that dietary administration of oltipraz, PEITC, alpha-tocopherol and beta-carotene, may exert chemopreventive effects in the digestive tract of the rat by enhancing GST, GPx, and, to a lesser extent, GSH levels.
Carcinogenesis 1996 Jul
PMID:Effect of oltipraz, alpha-tocopherol, beta-carotene and phenethylisothiocyanate on rat oesophageal, gastric, colonic and hepatic glutathione, glutathione S-transferase and peroxidase. 870 46


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