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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both dehydroepiandrosterone (DHEA) and the synthetic steroid 16 alpha-Br-epiandrosterone (Br-Epi), a more potent inhibitor of glucose-6-phosphate dehydrogenase (G6PDH) than DHEA, inhibit the 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulation of superoxide anion (O2-) formation by human neutrophils. DHEA has previously been shown to inhibit the development of spontaneous breast cancer and chemically induced tumors of the lung and colon as well as TPA promoted skin tumors in the mouse. The inhibition of TPA stimulated O2- formation by DHEA may contribute to the cancer preventive activity of this steroid.
Carcinogenesis 1985 Mar
PMID:Dehydroepiandrosterone and 16 alpha-Br-epiandrosterone inhibit 12-O-tetradecanoylphorbol-13-acetate stimulation of superoxide radical production by human polymorphonuclear leukocytes. 298

Some aspects of carbohydrate metabolism were investigated in three non-malignant, glycogen storing, cell lines derived from a primary culture of rat hepatocytes, and in the Morris hepatoma 3924 cells. The three cell lines show biochemical alterations which are, to a large extent, similar to those found in the hepatoma cells: increased activity of glycolytic enzymes and decreased activity of gluconeogenetic enzymes. An increase of glucose-6-phosphate dehydrogenase activity is also found. The three cell lines, as the Morris hepatoma cells, actively convert glucose into lactate under the in vitro conditions of culture. Fructose is not taken up as quickly as glucose and galactose is not metabolized. As compared with normal hepatocytes, the three cell lines have altered metabolism and growth behaviour. They largely resemble the preneoplastic cells appearing in rat liver at the early stages of experimental carcinogenesis.
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PMID:Study of carbohydrate metabolism in glycogen storing cell lines derived from cultured rat hepatocytes. 298 18

Mice were given i.v. injections of various tumor cell lines and, beginning 24 h later exposed for 3 weeks to 70% oxygen. Hyperoxia reduced the number of lung colonies derived from MT-7 cells (originally a mammary carcinoma) and of the lung-tumor derived cell lines 498 and Line-1 early passage. Lung colonies derived from Line-1 late passage, lines M109, B16-F10 and Lewis lung carcinoma were oxygen resistant. Lung metastases following i.m. injection of MT-7 cells were oxygen-sensitive and metastases derived from B16-F10 cells or Lewis lung carcinoma were oxygen resistant. Pre-exposure of mice for 48 h to 100% oxygen enhanced colony formation for all cell lines examined whereas exposure to 100% oxygen after i.v. injection only curtailed the growth of the cell lines previously shown to be sensitive to 70% oxygen. There was no correlation between oxygen sensitivity or resistance and the levels of total glutathione or activities of superoxide dismutase (SOD), glutathione reductase or peroxidase or glucose 6-phosphate dehydrogenase in the cell lines. However, upon injection in mice a resistant cell line increased its anti-oxidant defense mechanisms while growing in vivo whereas a sensitive cell line failed to show such adaptation.
Carcinogenesis 1988 Mar
PMID:Effects of hyperoxia on growth of experimental lung metastasis. 334 81

The carcinogenic efficiency of very low doses of N-nitrosodiethanolamine (NDELA), an N-nitroso compound of environmental significance, was assessed by administering it to male Sprague-Dawley rats at five different dose levels: 0.2, 0.63, 1.5, 6 and 25 mg/kg b.w./day in the drinking water. Quantitation of the numbers and size of liver foci positive for glucose-6-phosphate dehydrogenase (G6PDH) by morphometric methods revealed a good correlation between the dose and duration of carcinogen treatment and the extent of G6PDH-positive foci development. Thus the area density increased proportional to time and dose. The dose-time relation for the induction of 1% G6PDH-positive liver tissues assessed as a double logarithmic plot gives a straight line with the same characteristics as that which results when the induction of liver tumors is evaluated.
Carcinogenesis 1988 Apr
PMID:Dose-time relationship of the development of preneoplastic liver lesions induced in rats with low doses of N-nitrosodiethanolamine. 335 69

Benzidine (BZ) is a known animal and human carcinogen, and is mutagenic in the Ames test using strain TA 98. Several workers have shown that hepatic S9 fraction from hamster is much more effective than is rat S9, as an activation system for BZ in the Ames test. We show that rat microsomal fraction inhibits hamster S9 activation of BZ. Hamster microsomal fraction, supplemented with glucose-6-phosphate dehydrogenase (G6PdeH), gives a BZ dose-dependent mutagenic response, in the absence of cytosolic fraction. Rat microsomal fraction, in contrast, gives relatively little activation, under comparable conditions. Activation was enhanced when hamster or rat cytosol was added back to a mixture of hamster microsomes and G6PdeH. When strain TA 98 was replaced by strain TA 98/1,8-DNP6, very little activation of BZ was observed. Partially purified mouse liver acetyltransferase effectively activated BZ to mutagenic products in the presence of acetyl coenzyme A (CoASAc)/hamster microsomes/G6PdeH. Hamster and rat liver cytosol contain a CoASAc-dependent as well as a CoASAc-independent cytosolic activating factor of BZ. Hamster but not rat microsomal activation of BZ is enhanced in the presence of CoASAc. The biochemical mechanisms of BZ activation in the Ames test are discussed in light of these results.
Carcinogenesis 1987 Jan
PMID:Benzidine activation in the Ames test: roles of hepatic N-acetyltransferase and other cytosolic and microsomal factors. 354 72

Adenylate cyclase (AC) activity was demonstrated histochemically using adenylate-(beta,gamma-methylene)diphosphate as substrate in cryostat sections of livers from 45 rats treated for 7-10 weeks with N-nitrosomorpholine (NNM) (120 mg/l drinking water) and from nine untreated control rats. The enzyme patterns of normal tissue, preneoplastic and neoplastic lesions were characterized and correlated with the morphologically defined stages of tumour development in the liver. Light microscopically, the enzyme activity of normal tissue was restricted to the plasma membrane, and was most pronounced along the bile canaliculi of the hepatocytes. In glycogen storage foci and mixed cell foci induced by NNM no, or only very weak, AC activity was visible. In the cells of neoplastic nodules and hepatocellular carcinomas AC activity was also clearly reduced. However, in small parts of the plasma membrane which lined lumina resembling normal bile canaliculi and in cytoplasmic vesicles closely associated with these structures, some AC activity was occasionally detected by light and electron microscopy. Whereas the tissue of normal appearance surrounding the lesions showed a marked increase in AC activity in the presence of glucagon, forskolin and cholera toxin. AC activity in the preneoplastic and neoplastic liver lesions could not, or could only weakly, be stimulated by this treatment. As demonstrated in serial sections of the foci, the reduction in AC activity corresponded to changes in the activity of other enzymes studied earlier in the same model. Thus the reduction in AC activity was accompanied by a decrease in the activity of glucose-6-phosphatase and glycogen phosphorylase, and by an increase in the activity of glucose-6-phosphate dehydrogenase. The results support the concept that the focal changes in the activity of many enzymes (including those of carbohydrate metabolism) during hepatocarcinogenesis are the consequence of aberrations in superordinate regulatory mechanisms of cell metabolism.
Carcinogenesis 1986 Apr
PMID:Loss of adenylate cyclase activity in preneoplastic and neoplastic lesions induced in rat liver by N-nitrosomorpholine. 369 88

N-acetylcysteine (NAC) was administered to rats in various combinations with an enzyme inducer (Aroclor 1254) and with depletors of reduced glutathione (GSH), i.e., diethyl maleate (DEM) and buthionine sulfoximine (BSO). NAC increased intracellular glutathione levels in erythrocytes and in liver and lung cells, and replenished its stores following depletion. It did not affect the concentrations nor the spectral properties of cytochromes P-450 in hepatic and pulmonary microsomes, whereas it stimulated, especially in Aroclor-pre-treated animals, cytosolic enzyme activities involved in NADP reduction (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), in glutathione reduction (GSSG-reductase) and in the reductive detoxication of xenobiotics by-passing formation of reactive oxygen species (DT-diaphorase). In vivo treatment with the drug enhanced detoxication by liver and lung S-12 fractions of direct-acting mutagens (ICR 191, epichlorohydrin, 4-nitroquinolino-N-oxide and dichromate) and counteracted opposite effects triggered by administration of GSH depletors. The metabolic activation of procarcinogens (aflatoxin B1, 2-aminofluorene, cyclophosphamide, benzo[a]pyrene, a tryptophan pyrolysate product and cigarette smoke condensate) was inhibited by NAC in uninduced rats, while it was further stimulated in Aroclor-pre-treated animals. Additional assays, performed also with other enzyme inducers (phenobarbital and 3-methylcholanthrene) suggested that the effect of NAC on the metabolic activation of procarcinogens depends on the balance between an increased production of mutagenic metabolites (prevailing in induced animals) and their binding by intracellular thiols (prevailing under normal conditions). Thus, due to its dual role as a nucleophile and as a SH donor, NAC appears to exert protective effects by modulating glutathione metabolism and the biotransformation of mutagenic/carcinogenic compounds. This may have clinical relevance, since NAC is administered to individuals, such as cigarette smokers, who are more heavily exposed to GSH depletors and to carcinogenic agents.
Carcinogenesis 1985 Dec
PMID:In vivo effects of N-acetylcysteine on glutathione metabolism and on the biotransformation of carcinogenic and/or mutagenic compounds. 390 42

The effects of dietary administration of 3,5-di-tert-butyl-4-hydroxytoluene (BHT), 2(3)-tert-butyl-4-hydroxyanisole (BHA), ethoxyquin (EQ) and 5-(2-pyrizinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz) on aflatoxin B1 (AFB1) - DNA adduct formation in vivo in livers and kidneys of rats were investigated. Male F344 rats were treated with 1 mg/kg AFB1 by i.p. administration and nucleic acids isolated 2 h post dosing. Animals were fed a semipurified diet supplemented with either 0.5% EQ, 0.45% BHT, 0.45% BHA or 0.1% oltipraz for 2 weeks prior to AFB1 treatment. Analysis of nucleic acid bases by h.p.l.c. showed that several AFB1 metabolite-DNA adducts were formed in both tissues. The principal and related adducts of 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 represented approximately 80-90% of all adducts in both tissues and in all treatment groups. However, inclusion of the antioxidants in the diet resulted in substantial reductions in overall AFB1 modified DNA levels. EQ, BHT, BHA and oltipraz reduced the covalent binding of AFB1 to liver DNA by 91, 85, 65 and 76% and to kidney DNA by 80, 35, 62 and 64%, respectively. Concordantly, the specific activities of hepatic enzymes of presumed importance to AFB1 detoxification, epoxide hydrase, and glucuronyl and glutathione transferases were significantly elevated by all antioxidants. Reduced glutathione levels were unchanged except by oltipraz, although activities of enzymes contributing to the maintenance of reduced glutathione pools, glutathione reductase and glucose-6-phosphate dehydrogenase, were elevated in most treatment groups. An excellent correlation (r = 0.95) was observed between the degree of inhibition of DNA binding by AFB1 and the induction of hepatic glutathione S-transferase activities by the four antioxidants.
Carcinogenesis 1985 May
PMID:Modification of aflatoxin B1 binding to DNA in vivo in rats fed phenolic antioxidants, ethoxyquin and a dithiothione. 392 31

The endogenous synthesis of cholesterol in hepatocyte nodules, induced in male Wistar rats, by a single dose of the hepatocarcinogen diethylnitrosamine followed by a selection procedure, was investigated and was compared with that in surrounding and control tissue. In addition, the activity of enzymes related to carbohydrate metabolism (glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glucose-6-phosphatase and pyruvate kinase), was measured. Hepatocyte nodules showed a striking increase in their capacity for synthesizing cholesterol, in comparison to surrounding and control tissues, and an enhancement in the activity of the pentose phosphate pathway, as indicated by increased activity of glucose-6-phosphate dehydrogenase and of 6-phosphogluconate dehydrogenase, and a concomitant decrease of glucose-6-phosphatase. The stimulation of cholesterol synthesis and of the pentose phosphate pathway was associated with increased incorporation of labelled thymidine into DNA. These data indicate that, among other metabolic disturbances, enhancement of cholesterol synthesis and of the pentose phosphate pathway, is accompanied by an increased proliferative capacity of hepatocyte nodules.
Carcinogenesis 1985 Sep
PMID:Enhancement of cholesterol synthesis and pentose phosphate pathway activity in proliferating hepatocyte nodules. 402 34

The influence of sodium phenobarbital (PB) treatment on the sequence of N-nitrosomorpholine (NNM) induced focal preneoplastic lesions in the rat liver was investigated using a combined morphological and enzyme histochemical approach. Quantitative assessment of the different types of foci of altered hepatocytes visible in H&E sections after carcinogen application, namely the clear and acidophilic cell glycogen storage foci and mixed cell foci comprising glycogen storing cells and also more basophilic hepatocytes showing reduction in glycogen reserves, revealed a shift towards mixed cell character and greater size in PB-treated livers in comparison to those receiving NNM alone. Within the three dose levels of PB investigated (0.75, 0.075 or 0.0075 g/l drinking water) a clear dose dependence in appearance of mixed cell foci was apparent. Assessment of alterations in the activities of marker enzymes observed within preneoplastic foci was carried out by comparison of PAS preparations with sections reacted for glucose-6-phosphate dehydrogenase (G6PDH), gamma-glutamyl transpeptidase, glucose-6-phosphatase and adenosine triphosphatase. G6PDH proved the most consistent enzyme marker for small glycogen storage foci whereas larger foci of that type and mixed cell foci were associated with change in activity of all enzymes studied. The results are discussed in relation to the sequence of events occurring during hepatocarcinogenesis and the influence of PB on altered cellular populations. The applicability of enzyme markers is further considered in view of the question of heterogeneity within populations of preneoplastic foci.
Carcinogenesis 1983
PMID:Enhancement of NNM-induced carcinogenesis in the rat liver by phenobarbital: a combined morphological and enzyme histochemical approach. 613 86


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