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)

The early lesions which arise in the Syrian hamster pancreas prior to the appearance of carcinomas induced by treatment with the related carcinogens di-hydroxy-di-n-propyl nitrosamine or di-oxo-di-n-propyl nitrosamine were investigated in order to assess their roles in tumourigenesis. A sequence of events is proposed leading from ductal or ductular proliferations through regions of epithelial atypia (so-called dysplastic lesions) to carcinomas. This sequence appears distinct from that leading from ductular proliferations to benign multilocular cysts or cystadenomas. Radioautographic and histochemical evidence is presented supporting this proposal linking atypical proliferations but not cystic lesions with the induced carcinomas. Increase in the activity of glucose-6-phosphate dehydrogenase was established as being a good histochemical marker for early atypical proliferations during pancreatic carcinogenesis whereas gamma-glutamyl transpeptidase was found lacking in this respect. In addition, alteration in polysaccharide metabolism was observed during the development of the carcinomas.
Carcinogenesis 1983
PMID:Early lesions during pancreatic carcinogenesis induced in Syrian hamster by DHPN or DOPN. I. Histologic, histochemical and radioautographic findings. 618 49

Dehydroepiandrosterone (DHEA), a major adrenal secretory product in men and women, is a potent inhibitor of mammalian glucose-6-phosphate dehydrogenase (G6PDH). Long-term treatment with this steroid has previously been found to suppress spontaneous breast cancer development in C3H mice. DHEA is now shown to inhibit Epstein-Barr virus (EBV)-induced morphologic transformation and stimulation of DNA synthesis in human lymphocytes. 16 alpha-Br-epiandrosterone, a DHEA analog that is about 60 times as potent as DHEA as an inhibitor of G6PDH, is much more effective as an inhibitor of EBV-induced transformation.
Carcinogenesis 1981
PMID:Dehydroepiandrosterone and 16 alpha-bromo-epiandrosterone: inhibitors of Epstein-Barr virus-induced transformation of human lymphocytes. 626 30

The livers from a total of 51 Sprague-Dawley rats treated with different doses of N-nitrosomorpholine (80-120 mg/l in the drinking water) for up to 14 weeks together with the livers of 28 control animals were histochemically investigated at the cessation of carcinogenic insult and at varying periods thereafter for their glycogen content, basophilia and activities of various enzymes of carbohydrate metabolism: glycogen synthetase, glycogen phosphorylase, glucose-6-phosphatase, glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphate dehydrogenase. The enzymatic patterns of normal tissue, preneoplastic and neoplastic lesions were characterized and compared with reference to the morphologically defined stages of tumor development in the liver. The early appearing glycogen storing areas, localized in the peripheral and intermediate lobular regions, did not show significant changes in the histochemically demonstrable activities of the enzymes tested. After cessation of the carcinogen treatment the more pronounced glycogen storage foci which developed within the aforementioned regions of the liver acinus usually showed a reduction in the activities of phosphorylase and glucose-6-phosphatase while the activity of glucose-6-phosphate dehydrogenase, a key enzyme for the pentose phosphate pathway, was increased. The mixed cell foci, neoplastic nodules and tumors which emerged at later stages were characterized by a progressive shift away from glycogen metabolism towards glycolysis and the pentose phosphate pathway, as indicated by an increase in glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphate dehydrogenase activities. These changes in enzyme pattern are supportive of a developmental sequence leading from glycogen storage foci through mixed cell foci and neoplastic nodules to hepatocellular carcinomas.
Carcinogenesis 1982
PMID:Correlative histochemistry of some enzymes of carbohydrate metabolism in preneoplastic and neoplastic lesions in the rat liver. 629 53

Sprague-Dawley rats were treated with N-nitrosomorpholine (NNM) alone (7 weeks, 120 mg/l in drinking water), with NNM followed by phenobarbital (PB) (750 mg/l for 6 weeks) or PB alone. The livers from these animals were investigated for glycogen content and activities of glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, glycogen phosphorylase and glycogen synthetase. The following parameters proved to be significantly altered in the livers of rats treated with either NNM or PB or both compared with untreated controls: glycogen content was increased and the activities of glucose-6-phosphatase and glycogen synthetase were decreased. Although these data show some similarities in changes of glycogen metabolism of livers treated with NNM or PB, earlier histochemical investigations revealed important differences in the distribution of these alterations within the liver parenchyma.
Carcinogenesis 1983
PMID:Influence of phenobarbital on glycogen metabolism of rat liver pretreated with N-nitrosomorpholine. 630 40

N-Acetylcysteine (NAC), reduced (GSH) and oxidized (GSSG) glutathione were negative in the Ames test with 7 Salmonella strains, while L-cysteine was activated by rat liver S-9 fractions to metabolites mutagenic to strains TA102, TA97 and TA100. The mutagenic response in S. typhimurium strains (TA1535, TA98, TA100, TA102) and the levels of enzyme activities, responsible for NADP+ or GSSG reduction and for the utilization of NADPH or GSH in rat liver S-9 fractions, were investigated following in vitro preincubation of NAC with four direct-acting mutagens and six procarcinogens. Treatment with this nucleophilic and reducing compound resulted in a dose-related decrease of the direct mutagenicity of epichlorohydrin, hydrogen peroxide and, sharply, of 4-nitroquinolino-N-oxide and sodium dichromate. The mutagenicity of these compounds, both in the absence and in the presence of NAC, was decreased by rat liver S-9 fractions and to some extent by lung S-9 fractions. A diphasic effect was observed in the case of procarcinogens (cyclophosphamide, 2-aminofluorene, cigarette smoke condensate, Trp-P-2, aflatoxin B1 and benzo[a]pyrene), i.e., an enhancement of S-9 requiring mutagenicity at intermediate NAC doses, which could be ascribed to metabolic factors acting in vitro, and a loss of mutagenicity at high NAC doses, which could be ascribed to trapping of electrophilic metabolites. Out of the five S-9 enzyme activities under study, i.e., glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, malic enzyme, GSH peroxidase and GSSG reductase, only the last one showed significant changes following mutagen and/or NAC treatment.
Carcinogenesis 1984 Apr
PMID:In vitro effects of N-acetylcysteine on the mutagenicity of direct-acting compounds and procarcinogens. 636 36

Long-term treatment of C3H mice with the adrenal steroid, dehydroepiandrosterone (DHEA), has previously been shown to suppress spontaneous breast cancer development. A single i.p. injection of DHEA into C3H or ICR mice inhibits the rate of [3H]thymidine incorporation in breast epithelium and in 12-0-tetradecanoylphorbol-13-acetate (TPA)-stimulated epidermis. DHEA is a potent non-competitive inhibitor of mammalian glucose-6-phosphate dehydrogenase (G6PDH). 16 alpha-Br-epiandrosterone (Br-Epi), which is 60 times more active than DHEA is an inhibitor of G6PDH, is also much more active in reducing the rate of [3H]thymidine incorporation into mouse breast epithelium and epidermis. Synthetically prepared DHEA-sulfatide also inhibits G6PDH activity and [3H]thymidine incorporation in TPA-stimulated mouse epidermis. On the contrary, DHEA-sulfate, which is virtually inactive as an inhibitor of G6PDH, is also inactive as an inhibitor of [3H]thymidine incorporation in mouse epidermis.
Carcinogenesis 1981
PMID:Inhibition of DNA synthesis in mouse epidermis and breast epithelium by dehydroepiandrosterone and related steroids. 645 47

Persisting focal lesions, namely glycogen storage (glycogenotic) foci and mixed cell foci, were induced in liver by treatment of rats with the hepatocarcinogen N-nitrosomorpholine in a concentration of 200 mg/l drinking water for 7 weeks. Four and seven weeks after withdrawal of the carcinogen, the persisting foci were dissected from freeze-dried cryostat sections and their glycogen content and glucose-6-phosphate dehydrogenase activity were analyzed with highly sensitive luminometrical tests. The foci composed exclusively of storage cells contained on an average 100% more glycogen than the surrounding tissue of normal appearance or the liver parenchyma of untreated control animals. The overall glycogen content of the mixed cell foci, which were composed of both glycogenotic and glycogen-poor basophilic cells, was not distinguishable from that of the normal liver tissue. The activity of the G6PDH showed a clear tendency to higher values in the majority of the small glycogen storage foci (up to 100 ng dissected material). However, in larger glycogenotic foci and in particular in the mixed cell foci the activity of this enzyme was significantly higher (by a factor of approximately 3 and 6, respectively) than in the surrounding tissue of normal appearance and in the liver parenchyma of untreated controls. The data support the concept that hepatocarcinogens induce a focal hepatic glycogen storage disease of the liver which appears to elicit adaptive enzymatic changes gradually redirecting the disturbed carbohydrate metabolism towards other metabolic pathways, such as the pentose phosphate pathway.
Carcinogenesis 1984 Feb
PMID:Biochemical microanalysis of glycogen content and glucose-6-phosphate dehydrogenase activity in focal lesions of the rat liver induced by N-nitrosomorpholine. 669 43

The effects of 2-acetylaminofluorene (2-AAF), sodium phenobarbital (PB) and 4,4'-diaminodiphenylmethane (DDPM) on the developmental sequence of N-nitrosomorpholine (NNM) induced changes in the rat liver was investigated using a histological, histochemical and morphometric approach. Male Sprague-Dawley rats were treated with NNM for 3 weeks, maintained on basal diet for 1 week and then fed on diets containing either 0.005% 2-AAF, 0.05% PB, 0.08% DDPM or, as carcinogen controls, no addition (basal diet, BD) for a further 48 weeks. Control and experimental groups were sacrificed at weeks 4, 16, 28, 40 and 52 of the investigation. The incidence of the hepatocellular carcinomas observed at weeks 40 and 52 was markedly enhanced by 2-AAF treatment and slightly increased after PB administration. 2-AAF also exerted a positive influence on the development of angiosarcomas, benign hemangioendotheliomas and cystic cholangiomas. DDPM did not show clear effects on the development of liver cell carcinoma but enhanced the induction of cholangiofibromas, cholangiofibrosis and, very markedly, spongiosis hepatis. No neoplastic lesions were observed in animals treated with 2-AAF, PB or DDPM without prior application of NNM. Morphometric analysis of enzyme-altered foci revealed contrasting effects of 2-AAF, PB and DDPM, not only on number and size of lesion but also on their histochemical phenotype. Thus whilst 2-AAF administration was primarily linked with increase in number of lesions, PB appeared to stabilise their phenotypic cellular changes and increased the activity of G6PDH. DDPM did not significantly influence the number of focal lesions but seemed to effect a decrease in phenotypic alteration within foci. The results suggest that changes in the nature of enzyme-altered foci may be correlated with enhancement or inhibition of tumorigenesis.
Carcinogenesis 1984 Mar
PMID:Modification of the development of N-nitrosomorpholine-induced hepatic lesions by 2-acetylaminofluorene, phenobarbital and 4,4'-diaminodiphenylmethane: a sequential histological and histochemical analysis. 670 39

In an approach to testing the possible relationship between embryogenesis and carcinogenesis, we examined the susceptibility of rats carrying the grc, which is an MHC-linked gene complex affecting growth and development, to the development of the cellular and biochemical changes known to be associated with the induction of cancer. Genetically related strains which differed mainly by the presence or absence of the grc were fed a diet containing 0.02% N-2-acetylaminofluorene (AAF), and the induction of gamma-glutamyltranspeptidase (GGT)-positive foci, bile-duct proliferation and oval-cell proliferation in the livers of the two groups of animals were scored. All of the rats homozygous for the grc displayed GGT-positive foci (from three to six per section) and extensive bile-duct and oval-cell proliferation. By contrast, only 27% of the animals which did not carry the grc had GGT-positive foci in the liver, and these were present in smaller numbers (from one to three per section); there was no bile-duct or oval-cell proliferation. Biochemical studies of the liver and testes showed that the grc homozygotes had the metabolic abnormalities associated with the development of cancer: increased cholesterol biosynthesis; increased DNA synthesis, as indicated by an enhanced incorporation of 3H-thymidine into DNA; stimulation of the hexose monophosphate (HMP) pathway, as indicated by increased levels of glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD); and decreased levels of circulating lipoproteins. Both the morphological response of the rats carrying the grc to feeding AAF and the biochemical abnormalities that exist in these animal are consistent with the changes which eventually lead to cancer. Thus, there appears to be a relationship in rats between aberrations in the control of growth and development, susceptibility to the chemical induction of cancer and the control of cholesterol biosynthesis.
 ...
PMID:Enhanced susceptibility to a chemical carcinogen in rats carrying MHC-linked genes influencing development (GRC). 674 13

A comparative morphologic, morphometric and enzyme histochemical investigation of lesions induced by short-term application of N-nitrosomorpholine (NNM) and subsequent so-called 'selection pressure' was carried out in order to assess the characteristics of the numbers of induced putative preneoplastic populations and to cast light on reversibility associated with this model. The glycogen storage foci, mixed cell foci and neoplastic nodules observed after 'selection pressure' were in principle similar to those seen after stop experiments, although alterations in morphology and enzyme phenotype of individual cells were usually far more pronounced after short-term induction. It was established that 75% of the lesions were no longer visible 11 weeks after withdrawal of induction stimuli and that a large proportion of these remaining demonstrated heterogeneity in morphological and histochemical markers indicative of reversion to normal phenotype. After a further 10 weeks a slight increase in number of foci associated with decrease in size and enhanced homogeneity in phenotypic markers was established. The behaviour of foci and nodules undergoing reversion was considered with respect to changes in basophilia and glycogen storage and activity of the enzymes glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, glyceraldehyde 3-phosphate dehydrogenase, glycogen phosphorylase and synthase, acid phosphatase and gamma-glutamyl transpeptidase and correlated with location of altered cellular populations within the liver functional acinus.
Carcinogenesis 1983
PMID:Phenotypic instability in focal and nodular lesions induced in a short term system in the rat liver. 685 Sep 91


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