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

Nonimmunological defenses are very diverse in type. Some are directed against already transformed cells and belong to mechanisms of containment. Others exert a surveillance by preventing or inhibiting initial events of carcinogenesis. Chalones and oncolytic factors in sera and exudates are agents of containment. Under appropriate circumstances, the autoxidation of thiols and the formation of mixed disulfides lead to destruction of tumor cells in vitro and in vivo. Both processes involve the generation of superoxide radicals and of hydrogen peroxide which, in turn, activate the peroxide:peroxidase:halide system. Thiol:disulfide ratios and interchange codetermine the antioxidative activity of cellular membranes, thus bearing on carcinogenesis. Many aliphatic and aromatic antioxidants are endowed with anticarcinogenic properties. The fact that they are inhibitors of free radical processes corroborates the increasingly evident role of free radicals in carcinogenesis. Endogenous antioxidants and exogenous ones in foods are agents of surveillance. Antioxidant activity, linked with the ergastoplasm, points to a homeostatic mechanism that prevents self-accelerating chain reactions from leading to membrane damage or to carcinogenesis. Carcinogens can also be inactiviated by microsomal enzymes belonging to an overall mechanism of detoxification. Activity levels of these systems depend on diet and state of nutrition. They may be naturally very low, but they can be increased with various inducers.
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PMID:Nonimmunological host defenses: a review. 17 22

In the control animals of thyroid peroxidase is localized within the membrane of rough endoplasmic reticulum, perinuclear cisternae, microvilli, lamellar structures of the GOLGI apparatus and dispersed through the cytoplasm small vesicles. 3 weeks treatment of the animals with MTU leads to disappearance of the peroxidase activity from the follicular cells. However, a prolongation of MTU administration until the 6th month and latter causes a reappearance of the peroxidase activity within the same structures of the proliferating cells as in the control animals. In the epithelial cells of follicular and papillary carcinomas the reaction product is observed predominantly within the membrane of the rough endoplasmic reticulum, perinuclear space and outher membrane of the microvilli. The changes in the inhibitory effect of MTU on the peroxidase activity during thyroid carcinogenesis are discussed.
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PMID:Cytochemical localization of peroxidase activity in normal, proliferating and neoplastic thyroid tissues of rats. An ultrastructural study. 40 41

Lecithin and kephalin content in the microsomes and mitochondria of the rat liver, and also the activity of enzymatic and nonenzymatic systems of the phospholipid peroxidation showed a sharp change following 3,4-benzpyrene injection. Carcinogenesis is accompanied by significant changes in the lipid peroxides content and in the activity of the enzyme utilizing lipoperoxides (glutathion peroxidase, glutathion reductase). Accumulation of lipid peroxides in the rat liver in carcinogenesis was connected with disturbed balance of the generating systems and detoxication of lipid peroxides in the tumour is attributed to the high activity of the protective enzymatic systems and serves as a reflection of the adaptation mechanisms directed to the maintenance of a high pool of proliferating cells in the tumour.
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PMID:[Lipid peroxide metabolism in chemical carcinogenesis]. 42 80

Immunohistochemical evaluation of Cu, Zn- and Mn-superoxide dismutase (SOD) activity in various viral liver diseases was performed by the peroxidase-conjugated antibody indirect method. Anti-human Cu, Zn-SOD (rabbit) and anti-human Mn-SOD (guinea-pig) derived and purified from SOD of human erythrocytes and placentas were used to determine SOD distribution in liver tissues. SOD in the liver tissues was detected in 68 inpatients of our unit. They consisted of 23 cases with chronic hepatitis caused by hepatitis B virus (13) and hepatitis C virus (10), 24 with liver cirrhosis caused by hepatitis B virus (5) and hepatitis C virus (19) (15: compensatory, 9: decompensatory) and 21 with hepatocellular carcinoma caused by hepatitis B virus (2) and hepatitis C virus (18) complicated of liver cirrhosis. In viral liver diseases, SODs in the liver tissues were distributed to hepatocytes mainly in the pattern of cytoplasmic diffusion. The incidence of immunohistochemical Cu, Zn-SOD and Mn-SOD were 47.8% and 56.5% in chronic hepatitis, 93.3% and 86.7% in compensated liver cirrhosis, 11.1% and 22.2% in decompensated liver cirrhosis, respectively. The aggression of viral liver disease was accompanied with the decrease of SOD concentration in the liver tissues. Hepatocellular carcinoma cells were negative for Mn-SOD in all cases, and weakly positive for Cu, Zn-SOD in 2 out of 21 cases. Comparatively strongly positive SOD findings were obtained from normal regions neighboring carcinomas. A close relationship between the depletion of SOD in liver tissues and carcinogenesis in viral liver diseases was observed.
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PMID:Relationship between superoxide dismutase (SOD) and viral liver diseases. 132 May 79

Peroxidase in the presence of hydrogen peroxide catalyzes in vitro the activation of carcinogenic N,N-dimethyl-4-aminoazobenzene (DAB) to DNA-, tRNA- and homopolydeoxyribonucleotide-bound products. tRNA is the most susceptible to modification by the activated DAB. Binding of DAB products to macromolecules is inhibited by methyl viologen, nitrosobenzene, ascorbate, glutathione, NADH and MgCl2. The mechanism of these inhibitions was studied. The nuclease P1 version of the 32P-postlabeling assay was employed for detection and quantitation of some major DNA or tRNA adducts formed with DAB activated by a peroxidase system. tRNA modified by activated DAB shows a significantly increased acceptance for L-methionine.
Carcinogenesis 1992 Sep
PMID:Formation and 32P-postlabeling of DNA and tRNA adducts derived from peroxidative activation of carcinogenic azo dye N,N-dimethyl-4-aminoazobenzene. 139 52

We have developed and optimized an enzyme-linked immunosorbent assay (ELISA) for absolute quantitation of human beta-glucuronidase. This is a double antibody sandwich system employing two murine monoclonal antibodies specific for human beta-glucuronidase developed in our laboratories. The method involves (a) coating of the high binding polystyrene microtitration plate with the first antibody (7B6 IgG), (b) blocking of remaining active sites with 3% bovine serum albumin in phosphate-buffered saline, (c) application of samples, (d) addition of the biotinylated second antibody (6D2 IgG), (e) addition of streptavidin-horseradish peroxidase, and (f) development of color with o-phenylenediamine dihydrochloride-H2O2 and reading in a microplate reader at a wavelength of 490 nm. The method is highly sensitive with an optimal range of 10 to 100 ng/ml of the enzyme and is reproducible with intraday and interday precisions of 3.2 and 4.1%, respectively. The enzyme contents of 20 urine and 20 bile samples quantitated by this ELISA method were, respectively, 148 +/- 101 and 6380 +/- 3780 ng/ml (means +/- SD) which correlated well with their enzyme activities. Such a method for absolute quantitation of human beta-glucuronidase is essential for studying its pathophysiologic roles in cholelithiasis and carcinogenesis and can also be used clinically as an indicator for tissue damage or malignancy.
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PMID:Development and optimization of an enzyme-linked immunosorbent assay employing two murine monoclonal antibodies for absolute quantitation of human beta-glucuronidase. 141 87

In this work the resistance of peroxisome-proliferated hepatocytes to hydrogen peroxide (H2O2) has been studied. The question has been raised as to whether this resistance is a response to cytotoxicity. In an initial series of experiments, hepatocytes were isolated from rats that had been treated with nafenopin (NAF-hepatocytes). Isolated cells were exposed to a H2O2-generating system or to H2O2 in pulses. The ability to attach to collagen was used as a toxicological endpoint. Loss of attachment was found to be correlated to glutathione (GSH) depletion, and NAF-hepatocytes were more resistant to GSH depletion and to loss of attachment induced by H2O2 than were control hepatocytes. NAF-hepatocytes were not resistant to hydroquinone or to adriamycin. It was also indicated that this resistance was related to an altered metabolism of H2O2, less dependent on GSH. In a second series of experiments, hepatocytes from altered hepatic foci-bearing rats, treated with nafenopin or di(2-ethylhexyl)phthalate (DEHP), were used. This model was used in an attempt to monitor the development of resistance in different subpopulations of hepatocytes. It was found that the majority of hepatocytes developed resistance towards H2O2, and that, for example, foci marker-positive hepatocytes were as resistant as marker-negative cells. In control experiments with this model, it was found that marker-positive cells were more resistant towards diethyl maleate (DEM) or phorone than were marker-negative cells. In addition to demonstrating the validity of the model, these control experiments indicate an increased steady-state level of H2O2 in cells from peroxisome proliferator-treated rats. Other control experiments suggested that a low GSH-peroxidase activity protected from, rather than aggravated, the effect of peroxisome proliferation on marker-negative and GSH-depleted cells. It is concluded that H2O2 metabolism may affect the function of collagen receptors, but that a shift in H2O2 metabolism, so that it becomes less dependent on GSH, conferred resistance to this effect. The apparent non-focal induction of resistance to peroxisome proliferators, as opposed to the focal induction of resistance induced by most liver carcinogens, may explain the lack of development of gamma-glutamyltranspeptidase-positive foci in peroxisome proliferator-treated rats.
Carcinogenesis 1992 Oct
PMID:Peroxisome proliferation and resistance to hydrogen peroxide in rat hepatocytes: is development of resistance an adaptation to cytotoxicity? 142 34

The formation of thioether conjugates is an important pathway for inactivation of certain carcinogens. This study assessed the mechanism by which the bladder carcinogen 2-amino-4-(5-nitro-2-furyl)-thiazole (ANFT) forms a glutathione conjugate (ANFT-SG). Peroxidatic metabolism of ANFT, in the presence of glutathione, results in ANFT-SG formation. Both prostaglandin H synthase and horseradish peroxidase can catalyze this reaction. Metabolism of the reducing co-substrates ANFT, phenol, and aminopyrine elicit increases in oxidized glutathione (GSSG). ANFT-SG formation is potentiated by phenol and aminopyrine. tert-Nitrosobutane (tNB), a thiyl radical trap, prevented increases in both GSSG and ANFT-SG. Increasing concentrations of ANFT elicited corresponding increases in both GSSG and ANFT-SG. Peroxidatic metabolism of ANFT in the presence of glutathione, but not in the absence of glutathione, resulted in oxygen uptake. The formation of GSSG and oxygen uptake are consistent with the presence of thiyl radicals during ANFT metabolism. 5,5-Dimethyl-1-pyrroline N-oxide, a thiyl radical trap, was not as effective as tNB in inhibiting the formation of ANFT-SG and GSSG. Ascorbic acid, a reducing cosubstrate and antioxidant, was very effective in preventing ANFT-SG and GSSG formation, while the strong nucleophile methionine was ineffective. To clarify effects of different test agents, their effects on aminopyrine cation radical formation were assessed. Results are consistent with ANFT reacting with thiyl radicals to form ANFT-SG. ANFT appears to be a thiyl radical trap. Peroxidatic metabolism of ANFT probably results in the formation of a cation radical rather than a carbon-centered radical.
Carcinogenesis 1992 Nov
PMID:Mechanism of formation of the thioether conjugate of the bladder carcinogen 2-amino-4-(5-nitro-2-furyl)-thiazole (ANFT). 142 80

We reported previously that glutathione (GSH) is oxidized by peroxidases to a thiyl radical that can react with a number of chemicals, including the penultimate carcinogenic metabolite benzo[a]pyrene-7,8-dihydrodiol (7,8-B[a]PD), to give GSH conjugates. Here, we report that phenolic metabolites of benzo[a]pyrene (B[a]P) enhance the peroxidase-mediated formation of glutathione conjugates of 7,8-B[a]PD. The GSH conjugation of 7,8-B[a]PD in a horseradish peroxidase/peroxide system was increased over control values as follows: 9-OH-B[a]P by 4-fold, 7-OH-B[a]P by 3-fold, 1-OH-B[a]P by 2-fold. In contrast 3-OH-B[a]P was ineffective. A phenolic derivative of another polycyclic aromatic hydrocarbon (PAH), benz[a]anthracene, also enhanced GSH conjugation of 7,8-B[a]PD. The enhancement was dependent upon the presence of the phenol, horseradish peroxidase and peroxide. The phenolic compounds, including 3-OH-B[a]P, were also efficient reducing cofactors for the peroxidase. With the exception of 3-OH-B[a]P, the phenolic metabolites of PAH enhanced peroxidase-mediated formation of thiyl radical as detected by electron spin resonance spectrometry. Since both phenols and dihydrodiols are metabolites of B[a]P catalyzed by the cytochromes P450 system, enhancement of peroxidase-dependent 7,8-B[a]PD-GSH conjugation by phenols suggests a possible interaction between peroxidases and cytochromes P450 systems. This interaction may contribute to the detoxication of the penultimate carcinogenic PAH-dihydrodiols and other chemicals.
Carcinogenesis 1992 Apr
PMID:Peroxidase-mediated glutathione conjugation of benzo[a]pyrene-7,8-dihydrodiol is enhanced by benzo[a]pyrene phenols in vitro. 157 1

A 32P-postlabeling assay was employed for detection and quantitation of DNA adducts formed with carcinogenic 1-phenylazo-2-hydroxynaphthalene (Sudan I, Solvent Yellow 14) activated by a peroxidase system. Enrichment of adducts by digestion with nuclease P1 or by extraction into n-butanol prior to 32P-labeling was used. Both enrichment procedures exhibited comparable results for recovery of individual DNA adduct spots. Co-chromatographic analyses of adduct spots obtained by reaction with DNA and homopolydeoxy-ribonucleotides showed that four out of the eight major Sudan I-DNA adducts were formed by reaction of activated Sudan I with deoxyadenosine or deoxyguanosine in DNA. The accuracy of quantitation of adducts by 32P-postlabeling procedure is discussed.
Carcinogenesis 1992 Jul
PMID:32P-postlabeling analysis of adducts formed from 1-phenylazo-2-hydroxynaphthalene (Sudan I, Solvent Yellow 14) with DNA and homopolydeoxyribonucleotides. 163 90


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