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

In the present studies we have compared the levels of glutathione (GSH) and GSH-related enzymes in lung tumors and corresponding normal tissues obtained from the same individuals. We have also immunologically quantitated the relative amounts of glutathione S-transferase pi (or GST-P) type antigen in tumors and adjacent normal tissues from five patients. GST activities towards 1-chloro-2,4-dinitrobenzene (CDNB) and ethacrynic acid were found to be elevated in tumors from two out of five patients (patients #1 and 4), whereas the activity towards these substrates was markedly suppressed in the tumor tissue from one of the patients (#5). Immunotitration and Western blot studies using antibodies raised against pi-type GST isoenzymes of human lung and placenta indicated induction of GST pi-type isoenzyme in tumors from patients #1 and 4 and suppression of this isoenzyme in tumor from patient #5. The tumors from patients #2 and 3 did not show any increase in GST activity or GST pi-type antigen. Except for the tumor from patient #5, the GSH content was higher in the tumors from other patients. GSH reductase activity was found to be elevated in tumors of all the patients examined in this study. These results indicate that GSH and GSH related enzymes are differentially altered in lung tumors and GSH levels and GST pi- or GST-P-type isoenzyme(s) are not uniformly elevated in all tumors.
Carcinogenesis 1988 Sep
PMID:Glutathione S-transferase isoenzymes in human lung tumors. 340 73

A comparison of N-ethyl-N-hydroxyethylnistrosamine (EHEN)-induced preneoplastic and neoplastic lesions in the rat liver and kidney was made with respect to the expression of different drug metabolizing enzymes. Four cytochrome P-450 species (cyt. P-450 UT50, PB3a, MC1 and MC2) and microsomal epoxide hydrolase (mEHb) were investigated along with two glutathione S-transferase species (GST-P and A forms) earlier shown to be elevated in putative preneoplastic lesions in the liver and kidney, respectively. In contrast to the liver lesions, which showed clear decrease in all forms of cyt. P-450s and increase of mEHb, elevated levels of cyt. P-450 PB3a and, to a lesser extent, the other P-450 forms and early elevation to late decrease in mEHb characterized the renal tubular lesions. Thus opposite shift in enzyme phenotype was observed in carcinogen-induced focal lesions of the two organs. Variation in binding levels in the different nephron segments and zones of the liver acinus indicated physiological specialization with regard to the enzymes investigated and suggested that the altered phenotype of preneoplastic populations might be of adaptive significance.
Carcinogenesis 1987 May
PMID:Immunohistochemically demonstrated altered expression of cytochrome P-450 molecular forms and epoxide hydrolase in N-ethyl-N-hydroxyethylnitrosamine-induced rat kidney and liver lesions. 358 29

Glutathione transferase (GST) activity in the cytosolic fractions of four renal cortex tumors was found to be lower (1.85-3.4 times) than that present in the corresponding non-tumor cytosolic fractions. Glutathione transferase of both tumor and non-tumor kidney was purified by affinity chromatography and separated into five peaks at pH 4.7, 8.0, 8.4, 8.7 and 9.0 by isoelectric focusing. In the chromatogram of tumor tissues, the activity associated with the 'acidic' peak increased significantly, whereas the activities associated with 'basic' peaks all decreased in comparison with the corresponding peaks of non-tumor tissues. The acidic GST of human kidney is immunologically identical to GST pi, confirming that it is a good marker for human tumors.
Carcinogenesis 1987 Jun
PMID:Alteration of glutathione transferase isoenzyme concentrations in human renal carcinoma. 360 86

The mechanisms by which diallyl sulfide (DAS), a component of garlic oil, inhibits hepatocarcinogenicity of 1,2-dimethylhydrazine (DMH) were examined in male Fischer 344 rats. Rats were subjected to partial hepatectomy to stimulate hepatocellular proliferation required for initiation by DMH (50-200 mg/kg i.p.) given 12 h later. Initiation was assessed by the numbers of foci and nodules of hepatocytes that were positive for gamma-glutamyl transpeptidase (gamma-GT) or glutathione-S-transferase-P (GST-P) after 6 weeks promotion by orotic acid (1% in semi-purified diet). DAS at doses above 50 mg/kg (by gavage) administered 1 h before DMH (50 mg/kg) partially reduced the numbers of gamma-GT and GST-P-positive foci. By comparison, all doses of DAS (25-100 mg/kg) completely prevented liver necrosis by DMH (200 mg/kg). DAS substantially reduced macromolecular binding of [14C]DMH in cultured liver cells, but had no effect on their levels of glutathione-S-transferase, glutathione reductase or glutathione peroxidase at 18 h. These findings suggest that low dosages of DAS which reduce DMH binding appear more likely to inhibit hepatocarcinogenicity by reducing the promoting influences of post-necrotic regeneration than by preventing initiation.
Carcinogenesis 1987 Aug
PMID:Inhibition of hepatocarcinogenic responses to 1,2-dimethylhydrazine by diallyl sulfide, a component of garlic oil. 360 98

The effects of linolic acid hydroperoxides (product A) and secondary oxidative products of product A (product B), were examined in an in vivo mid-term test for hepatocarcinogens or hepatopromoters in rats. The number of placental type of glutathione S-transferase (GST-P)-positive foci of the liver was significantly reduced in rats given diethylnitrosamine (DEN) followed by products A (4.64 +/- 1.09, P less than 0.05) or B (3.62 +/- 1.65, P less than 0.01) as compared to the controls given carcinogen alone (6.31 +/- 2.82). The area of GST-P positive foci was also significantly reduced in rats given DEN followed by product B (0.30 +/- 0.21, P less than 0.05) as compared to the controls (0.47 +/- 0.23). These results suggest that linolic acid hydroperoxides or their secondary oxidative products are not hepatocarcinogens and rather may possess inhibitory potential for liver carcinogenesis.
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PMID:Inhibition of glutathione S-transferase P type-positive foci development by linolic acid hydroperoxides and their secondary oxidative products in a rat in vivo mid-term test for liver carcinogens. 373 30

Immunohistochemical investigation of liver tissue 48 h after single doses of the hepatocarcinogens diethylnitrosamine (DEN), dimethylnitrosamine, aflatoxin B1 and methylazoxymethanol acetate revealed the generation of a population of single glutathione S-transferase placental form (GST-P) positive hepatocytes. Yield was carcinogen dose dependent. Although the mixed function enzyme inducers sodium phenobarbital (PB), methylcholanthrene (Mech), polychlorinated biphenyls (PCB) and isosafrole (IS) did not in themselves induce comparable single cell lesions, their application prior to DEN caused significant alteration in the resultant numbers of GST-P positive hepatocytes observed. While PB and IS were associated with decreased yield, Mech and PCB, in contrast, brought about an increase. The results gained from investigation of the effects of 3-aminobenzamide administration and partial hepatectomy carried out at different times after carcinogen treatment also pointed to an 'initiated' character for the lesions and suggest that GST-P may be a useful marker for analyzing factors relevant to the initiation stage of hepatocarcinogenesis. Thus the interplay between carcinogen metabolism, DNA adduct formation and repair, toxicity and proliferation may be assessable in terms of numbers of enzyme-altered solitary hepatocytes.
Carcinogenesis 1987 Mar
PMID:Single GST-P positive liver cells--putative initiated hepatocytes. 381 43

Immunohistochemical staining using antirat glutathione S-transferase placental form (GST-P) rabbit antibody demonstrated marked binding to cells of putative preneoplastic lesions induced in both the liver and pancreas of Syrian hamsters by dihydroxy-di-n-propylnitrosamine treatment, whereas background normal-appearing tissue was negative. Thus, a protein showing immunological cross-reaction with rat GST-P is also elevated during pancreatic carcinogenesis and hepatocarcinogenesis in the hamster, suggesting its usefulness as a marker with potential relevance to the mechanisms underlying the neoplastic process.
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PMID:A protein cross-reacting immunohistochemically with rat glutathione S-transferase placental form as a marker for preneoplasia in Syrian hamster pancreatic and hepatocarcinogenesis. 391 5

Two cytochromes P450 (PB1 and PB2) have been isolated from the livers of rats treated with phenobarbital. PB2 (mol. wt. 53 500) is novel and is the first example of a phenobarbital-inducible enzyme with a Soret peak at 447 nm. Using an enzyme-linked immunosorbent assay, some immunochemical and structural similarities were observed between these cytochromes. PB1 and PB2 were induced by phenobarbital, Aroclor 1254, trans-stilbene oxide and to a lesser extent by isosafrole. Immunohistochemical localization of these proteins in the liver of untreated rats showed PB1 to be localized in a large area and PB2 in a narrow range of cells around the central vein. This demonstrates the heterogeneity of hepatocytes even within the centrilobular area and indicates that the synthesis of these two proteins is regulated differently although both are induced by the same agent, phenobarbital. Two 3-methylcholanthrene inducible cytochromes MC1 (mol. wt. 54 500) and MC2 (mol. wt. 57 000) were present at very low levels, MC2 mostly in the periportal region but also diffusely distributed throughout the lobule including some centrilobular cells, MC1 concentrated in the centrilobular region. The localization of two major groups of glutathione transferases (GST's) was also different. 'C' type proteins (Yb Yb') and microsomal epoxide hydrolase (EH), were concentrated around the central vein, whereas the 'B' type proteins (Ya Yc) and cytochrome P450 reductase were distributed in a larger area of this region. Thus, the localization was different for some members of the same enzyme family, whilst similarities in the localization existed across the border of the families: (i) PB2, MC1, EH and GST 'C' type proteins were concentrated in a narrow area around the central vein; (ii) PB1 and GST 'B' type proteins occupied a large centrilobular area; (iii) MC2 levels were very low, predominantly periportal but also diffusely distributed throughout the lobule. Treatment of the animals with inducers increased the staining intensity and in several cases extended the areas of cells containing these proteins over the adjacent zone without fundamentally altering their distributions. However, treatment with beta-naphthoflavone led to a shift of MC1 to the periportal area. This suggests that the expression of these proteins in certain cells is not an irreversible quality of differentiation but depends on the degree of suppression and derepression of regulatory components.(ABSTRACT TRUNCATED AT 400 WORDS)
Carcinogenesis 1984 Aug
PMID:Characterization, localization and regulation of a novel phenobarbital-inducible form of cytochrome P450, compared with three further P450-isoenzymes, NADPH P450-reductase, glutathione transferases and microsomal epoxide hydrolase. 643 May 87

The effect of dietary 2(3)-tert-butyl-4-hydroxy-anisole (BHA) alone and in combination with intraperitoneal injections of 3-methylcholanthrene (MC), on hepatic enzyme activities and benzo[a]pyrene (BP) metabolism was compared in male and female NMRI mice. In general, the characteristic induction pattern following dietary BHA administration in female mice could also be seen when male mice were used. The increase in epoxide hydrolase and cytosolic glutathione S-transferase following BHA feeding was however not as pronounced in males as in females. Also, MC treatment appeared to counteract the induction of GST activity to BHA in females but had no such effect in males. Liver microsomes from untreated male mice catalyzed the metabolism of BP less efficiently than did microsomes from females. BHA treatment increased this activity in both sexes to a comparable extent and the overall activity was the same in males and females having received MC. The pattern of BP metabolites was altered following BHA treatment. In general, an increase in BP-4,5-diol and a decrease in 9-OH-BP was observed. This pattern was also noticed when microsomes from MC treated and MC + BHA treated animals were compared. MC treatment alone increased the amount of BP-7,8-diol, the quinones and the phenols. The present report indicates that several factors may contribute to the response to dietary BHA in mice. Whether this has any consequence in regard to this compounds's anticarcinogenic effect remains to be elucidated.
Carcinogenesis 1982
PMID:Differential effects of dietary BHA on hepatic enzyme activities and benzo[a]pyrene metabolism in male and female NMRI mice. 706 33

The membrane and cytosolic protein phosphorylation patterns in the early stages of diethylnitrosamine-induced rat liver carcinogenesis, promoted by 2-acetylaminofluorene in the diet plus partial hepatectomy (DEN-AAF-PH), were analyzed by two-dimensional gel electrophoresis in animals fed a low protein (5% casein) diet, or the original high protein (24% casein) diet, in order to modulate the development of GST-P-positive preneoplastic lesions. Compared with untreated controls, membrane and cytosolic protein phosphorylation patterns changed only slightly in low protein-fed rats 7 days post-hepatectomy, with no appearance of enzyme-altered hyperplastic foci in the liver sections. By contrast, high protein-fed animals demonstrated GST-P-positive preneoplastic lesions 7 days post-hepatectomy and several acidic and more basic high M(r) phosphorylated membrane (between 97 and 116 kDa) as well as cytosolic (between 97 and 200 kDa) proteins could be detected. In the presence of enzyme-altered hepatocytes in the liver sections, low protein-fed rats demonstrated at 60 days post-hepatectomy cytosolic protein phosphorylation patterns remarkably similar to those shown by 24% casein-fed animals at 7 days post-hepatectomy, suggesting close correlation between protein phosphorylation patterns and development of preneoplastic lesions during the early stages of DEN-AAF-PH liver carcinogenesis. This may arise by a constitutive activation of one or more signal transduction pathways, possibly involving protein kinase C, during liver tumour promotion.
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PMID:Membrane and cytosolic protein phosphorylation patterns in the early stages of DEN-induced hepatocarcinogenesis in rats fed a high or low protein diet. 749 66


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