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)

Testosterone, testosterone propionate, 17 beta-trenbolone and progesterone, which represent the main endogenous and synthetic androgens and a progestin, were evaluated for possible cell transformation and genetic effects in Syrian hamster embryo (SHE) cells. Cell growth was reduced by treatment with the steroids at 10-30 micrograms/ml in a dose-related manner. Testosterone and testosterone propionate were less toxic than the other two steroids. Testosterone, testosterone propionate and progesterone induced morphological transformation of SHE cells with similar transformation frequencies. The most potent effects were observed with testosterone propionate, which induced cell transformation at 1-30 micrograms/ml in a dose-related manner. Testosterone and progesterone transformed cells only at the highest dose (30 micrograms/ml). 17 beta-Trenbolone did not induce a statistically significant level of cell transformations at any dose tested (up to 30 micrograms/ml). The transformation frequencies induced by testosterone, testosterone propionate and progesterone were less than one-half that induced by benzo[a]pyrene at 1 microgram/ml. None of these steroids induced significant increases in frequencies of chromosome aberrations or aneuploidy. Gene mutations were not observed for testosterone at the HPRT or Na+/K+ ATPase locus. Because these steroids are also associated with carcinogenic activity in vivo, these in vitro findings provide a model and new insights into the study of the mechanisms of androgen- and progestin-induced cell transformation.
Carcinogenesis 1995 Jun
PMID:Effects of testosterone, testosterone propionate, 17 beta-trenbolone and progesterone on cell transformation and mutagenesis in Syrian hamster embryo cells. 778 50

Using light microscopy enzyme cytochemistry to localize catalase activity in peroxisomes, a population of peroxisome-negative hepatocytes was detected in livers of rats during liver regeneration induced by two-thirds partial hepatectomy. However, examination by electron microscopy revealed that this population of hepatocytes contained peroxisomes with a delimiting membrane and a nucleoid, but no cytochemically demonstrable catalase activity within their matrix. Regenerating livers 6, 18, 24, 36, 48 and 72 hours, and 1 week after partial hepatectomy showed hepatocytes without catalase activity. However, their numbers varied, with the most numerous appearing at 24 hours after partial hepatectomy. Mitosis of catalase-negative hepatocytes were seen along with mitosis of hepatocytes containing the normal complement of catalase-positive peroxisomes. The catalase-negative hepatocytes did not show evidence of apoptosis or necrotic cell death. Lysosomal acid phosphatase activity and bile canalicular ATPase activity were present in hepatocytes with catalase-negative peroxisomes. Another population of hepatocytes with a small number of catalase-positive peroxisomes appeared and were more numerous at 36 hours after partial hepatectomy; ultrastructurally, these hepatocytes contained both catalase-negative peroxisomes, which appeared to undergo dissolution, and catalase-positive peroxisomes, which were smaller in size. After complete restoration of the liver, all hepatocytes displayed essentially uniform numbers of catalase-positive peroxisomes. These studies indicated that during liver regeneration there is a transient loss of catalase in peroxisomes of some hepatocytes. These cells proliferate and with time acquire new catalase-positive peroxisomes. The observations are discussed in relation to peroxisome biogenesis, hepatocellular carcinogenesis, and oxidative stress during liver regeneration.
 ...
PMID:Catalase-negative peroxisomes: transient appearance in rat hepatocytes during liver regeneration after partial hepatectomy. 788 49

Rat liver cytosolic hydroxysteroid sulfotransferases form highly reactive sulfuric acid esters from some benzylic alcohols, such as 1-hydroxymethylpyrene. In this study we examined the expression of hydroxysteroid sulfotransferase a (STa) in carcinogen-induced enzyme-altered, presumably preneoplastic, rat liver foci. Female Wistar rats were given a single i.p. injection of diethylnitrosamine (0.15 mumol/g body wt) 1 day after birth to induce the liver foci. After weaning, rats were given 1-hydroxymethylpyrene or phenobarbital continuously in their diet (250 or 500 p.p.m. respectively) for a total of 120 days. Carcinogen-induced liver foci were identified by a change in the marker enzyme adenosine triphosphatase. Immunohistochemical staining of consecutive sections using an anti-STa rabbit antibody demonstrated that STa was expressed at decreased levels in most of the adenosine triphosphatase-negative liver foci. This effect was observed in both 1-hydroxymethylpyrene- and phenobarbital-treated animals. The decrease in STa content in enzyme-altered foci may lead to a selective advantage of the preneoplastic cells in the presence of agents that are able to form reactive sulfuric acid esters, such as 1-hydroxymethylpyrene. In some diethylnitrosamine/phenobarbital-treated rats, a small number of atypical foci were observed, most of them showing enhanced expression of STa and unchanged to moderately increased ATPase activity.
Carcinogenesis 1993 Nov
PMID:Development of hydroxysteroid sulfotransferase-deficient lesions during hepatocarcinogenesis in rats. 824 53

A function for topoisomerases I and II in DNA excision repair can be postulated from the organization of the mammalian chromosome, involving nucleosomal structures and matrix-attached DNA loops. To analyse this function we determined UV-induced DNA incision in confluent human fibroblasts in the presence of 16 inhibitors of topoisomerases I and II which belonged to at least five different drug categories, based on their mechanism of action. Dose-response experiments were performed, analysed by linear regression and the concentrations at which DNA-incising activity was reduced to 50% were calculated (K50 values). The majority of these values represent concentrations for which interfering cell toxicity could be excluded. K50 concentrations, which were determined by extrapolating dose-response data, may hit the toxicity range, nevertheless, we deem our K50 scale useful for making biochemical comparisons. With respect to topoisomerase I, camptothecin and topotecan diminished repair-specific DNA incision to a small extent, whereas distamycin, which binds to the minor groove of DNA, caused a stronger effect. With respect to topoisomerase II the results were as follows. (i) The DNA intercalator ethidium bromide decreased DNA-incising activity at rather low concentrations, which indicates marked inhibitory potency. Quinacrine was less effective. (ii) Inhibitors intercalating and binding to the 'cleavable' DNA-topoisomerase complex (m-AMSA, mitoxantrone, doxorubicin and daunorubicin) strongly suppressed reparative DNA incision. (iii) Only small effects were observed using several drugs which act by trapping the 'cleavable' DNA-enzyme complex, namely nalidixic acid and oxolinic acid. In contrast, etoposide and teniposide inhibited post-UV DNA cleavage sizeably. (iv) Merbarone had to be applied at very high concentrations to reduce UV-induced DNA incision. (v) Novobiocin, an inhibitor of the ATPase subunit of topoisomerase II, markedly diminished repair-specific DNA cleavage. A comparison of the K50 values for DNA incision with those for DNA repair synthesis (1) shows that the majority of the investigated drugs inhibited both repair parameters. There were, however, differences in the concentrations required to achieve the 50% inhibition level. The results are best explained by assuming that in UV-irradiated human fibroblasts the 180 kd form of topoisomerase II is a target enzyme for inhibitors which suppressed repair and that this isozyme is involved in steps preceding repair-specific DNA incision.
Carcinogenesis 1993 Nov
PMID:Various inhibitors of DNA topoisomerases diminish repair-specific DNA incision in UV-irradiated human fibroblasts. 824 65

The effects of prolonged administration of the diuretic amiloride on pancreatic carcinogenesis induced by azaserine and on the labeling index of carcinogen-induced pancreatic lesions were investigated in Wistar rats. Rats were given 25 weekly injections of 10 mg/kg body weight azaserine and also 5 mg/kg body weight amiloride every other day until the end of the experiment at week 62. Carcinogen-induced pancreatic lesions were examined by histochemical techniques and were classified as ATPase-positive or ATPase-negative. In week 62, quantitative histologic analysis showed that prolonged administration of amiloride significantly reduced the number and size (as percent of parenchyma) of ATPase-positive pancreatic lesions, which are closely correlated with the subsequent development of pancreatic cancer. Amiloride also significantly decreased the labeling index of carcinogen-induced pancreatic lesions, but not of the surrounding acinar cells. In contrast, amiloride has no significant influence on the number and size of ATPase-negative pancreatic lesions. These findings indicate that amiloride inhibits pancreatic carcinogenesis, and that this effect may be related to the reduction of ATPase-positive lesions and to amiloride's inhibition of cell proliferation in neoplastic lesions of the pancreas.
 ...
PMID:Inhibition by amiloride of experimental carcinogenesis induced by azaserine in rat pancreas. 882 43

In an attempt to seek out new factors that are related to colorectal carcinogenesis at the molecular level, subtractive hybridization between cDNA of normal mucosal tissues and mRNA of colorectal carcinoma tissues was performed. Subsequent screenings of the cDNA libraries, constructed from normal mucosal tissues, using the "subtractive probes" generated a total of 46 clones that were expressed in normal mucosa but were either expressed at a significantly reduced level or not expressed at all in cancer tissues. Partial nucleotide sequences of all of these cDNA clones were determined, and sequence homology analyses were performed with the Genbank database. Of the 46 cDNA samples, 44 contained substantial sequence homologies with 32 immunoglobulin gene fragments, a helix-loop-helix basic phosphoprotein gene, an acidic ribosomal phosphoprotein P2 gene, a BLR1 gene for Burkitt's lymphoma receptor 1 gene, D5S419 DNA segment containing (C-A) repeats, a glucokinase (GCK) gene, a Na+, K+-ATPase alpha-subunit gene, a histocompatibility system HLA-DR heavy-chain gene, a dystrophic gene, a mucin (MUC2) gene, a mu-glutathione S-transferase gene, a Menkes disease protein gene, and a 40-kDa keratin intermediate filament precursor gene. The remaining two cDNA clones (now registered under GenBank accession numbers U17714 and U20428) showed few (less than 60%) sequence homologies with any known sequences in the GenBank database and, therefore, may represent novel genes whose expression was down-regulated in human colorectal carcinomas. The possible clinical significance of these findings and the involvement of these two genes in the carcinogenesis of colorectal as well as other cancers are being investigated.
 ...
PMID:Characterization of colorectal-cancer-related cDNA clones obtained by subtractive hybridization screening. 929 8

We have performed differential display comparing gene expression from cell lines derived from human colorectal tumors. The cell lines were selected for study based on their ability to form metastases following injection into athymic mice. One gene which was expressed exclusively by the metastatic lines was identified as human acylphosphatase (e.c. 3.6.1.7, acylphosphate phosphohydrolase). The expression of this gene was confirmed by RT-PCR using gene-specific primers. This gene product catalyzes the hydrolysis of phosphorylated intermediates of Na+/K(+)-ATPase and of Ca(2+)-ATPases of mammalian cells. Changes in the activity of the Na+/K(+)-ATPase pump, regulated by acylphosphatase, have been previously reported in chemically-induced colonic tumors. The differential expression of this gene in the human metastatic colorectal lines suggests it may be involved in the metastatic phenotype.
Carcinogenesis 1997 Dec
PMID:The expression of acylphosphatase is associated with the metastatic phenotype in human colorectal tumors. 945 Apr 95

Reactive oxygen species (ROS) and reactive metabolic intermediates generated from various chemical carcinogens are known to play an important role in cell damage and in the initiation and progression of carcinogenesis. Many radical scavengers, interestingly naturally occuring antioxidants have been found to be effective in inhibiting the induction of carcinogenesis by a wide variety of chemical carcinogens. Studies have also indicated that various spice principles form an important group as antioxidants. In the present study our goal was to investigate whether piperine an pungent principle of black and long peppers was able to inhibit or reduce the oxidative changes induced by chemical carcinogens in rat intestinal model. Carcinogenesis was initiated in intestinal lumen of male rats with 7,12,dimethyl benzanthracene, dimethyl amino-methyl azobenzene and 3-methyl cholenthrene. Oxidative alterations were assessed by determining thiobarbituric reactive substances, mainly malonaldehyde (as a measure of lipid peroxidation), thiol status and expression of gamma-GT and Na+-K+-ATPase activity in intestinal mucosa. Data indicated that carcinogens treatment induced GSH depletion with substantial increase in thiobarbituric reactive substances and enzyme activities. Piperine treatment with carcinogens resulted in inhibition of thiobarbituric reactive substances. It mediated a significant increase in the GSH levels and restoration in gamma-GT and Na+-K+-ATPase activity. The studies thus indicate a protective role of piperine against the oxidative alterations by carcinogens. It may be suggested that piperine modulates the oxidative changes by inhibiting lipid peroxidation and mediating enhanced synthesis or transport of GSH thereby replenishing thiol redox.
 ...
PMID:Piperine modulation of carcinogen induced oxidative stress in intestinal mucosa. 987 61

The frequency of oxidative base damage, such as 8-hydroxyguanine (8-OH-Gua), was determined at the nucleotide level of resolution using the ligation-mediated PCR technique. Administration of a renal carcinogen, ferric nitrilotriacetate (Fe-NTA), is known to induce oxidative stress and subsequent formation of 8-OH-Gua in the rat kidney. Whole genomic DNA was isolated from the rat kidney after or without Fe-NTA treatment and then cleaved with hot piperidine. In order to assess the frequency of 8-OH-Gua formation, we chose three genes, the tumor suppressor gene p53, the heat shock protein 70 (HSP70-1) gene and the Na,K-ATPase alpha1 subunit gene. No alteration in the cleavage profile was observed in the p53 and HSP70 genes after Fe-NTA treatment. In the case of the p53 gene, a low incidence of point mutations has been observed in this carcinogenesis system. On the other hand, time-dependent alterations, corresponding to the time course of overall 8-OH-Gua formation and repair, were detected in the promoter region of the Na,K-ATPase alpha1 subunit gene. GpG and GpGpG in specific regions seem to be hotspots for the formation of 8-OH-Gua. These results were confirmed by formamidopyrimidine-DNA glycosylase-dependent DNA cleavage patterns. Thus, oxidative base damage, such as 8-OH-Gua, was not distributed uniformly along the whole genome, but seemed to be restricted to particular genes and regions.
Carcinogenesis 1999 May
PMID:Analysis of 8-hydroxyguanine in rat kidney genomic DNA after administration of a renal carcinogen, ferric nitrilotriacetate. 1033 1

We previously demonstrated that rats exposed to the peroxisome proliferator (PP) diethylhexylphthalate (DEHP) had reduced serum ceruloplasmin (CP) oxidase activity, which suggests tissue copper deposition. Copper is highly toxic in excess, and results in cellular damage and hepatocellular carcinomas (HCC). This study addresses changes in expression of copper-related genes and metal accumulation in hyperplastic liver and tumors induced by PP. Male rats were fed diets containing DEHP or clofibrate (CLF) for 3-60 days (hyperplasia) and 4-chloro-6-(2,3 xylidino)-2-pyrimidinyl-thio(N-beta-hydroxyethyl) acetamide for 10 months (HCC). During hyperplasia, an immediate and progressive decrease in serum CP activity was observed (P < 0.05), as were reductions in mRNA levels for both CP and Wilson's disease gene (WD gene, a P-type ATPase) (P < 0.05). Tumor-bearing rats had lower serum CP activity (P < 0.05), and CP and WD gene mRNA levels were reduced in tumors (P < 0.05), and in liver surrounding tumors (SL) (P < 0.05). Metallothionein mRNA showed no consistent changes during hyperplasia. Tumors showed a 2.5-fold induction of metallothionein mRNA (P < 0.05), and a 1.2-fold increase in SL. Temporal increases in liver copper content occurred during hyperplasia, with increases of 2-fold (DEHP) and 3.3-fold (CLF) at 60 days (P < 0.05). Copper content was 2.2-fold higher in tumors (P < 0.05) and 1.7-fold higher in SL; iron did not increase and zinc decreased temporally. Thus, copper accumulation and changes in copper-related gene expression may be contributing factors in liver neoplasia in PP-treated rats. Loss of CP results in decreased free radical scavenger capacity and thus may enhance oxidative damage induced by PPs.
Carcinogenesis 1999 Jun
PMID:Hepatic hyperplasia and cancer in rats: alterations in copper metabolism. 1035 93


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