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)

Environmental lung injury may take the form of acute tracheobronchitis, asthma, pulmonary edema, chronic bronchitis, emphysema, allergic pneumonitis, fibrosing alveolitis, pleurisy, and neoplastic disease. Environmental factors eliciting these responses include irritant gases and fumes, oxidants, organic allergens, inorganic dust, bacterial enzymes, and high partial pressures of oxygen. The basic pulmonary reactions to these toxic agents--bronchoconstriction, vasoconstriction, increased vascular permeability, inflammation, carcinogenesis--may be mediated, aggravated, or modulated by biologically active substances. These humoral agents include biogenic amines (e.g. histamine): peptides (e.g., bradykinin, vasoactive intestinal peptide, and spasmogenic lung peptide); enzymes (e.g., proteases, superoxide dismutase, and mixed function oxidases); and acidic lipids (e.g., prostaglandins, prostaglandin endoperoxides, and thromboxanes).
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PMID:Environmental injury of the lung: role of humoral mediators. 35 83

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

Fecapentaenes form a class of potent fecal mutagens and have been suggested to play an initiating role in colon carcinogenesis. Although several indications have been found that fecapentaenes may induce oxidative DNA damage as well as DNA alkylation, the mechanism of genotoxicity remains unknown. In this study, electron spin resonance spectroscopy with several spin traps has been used in order to determine whether reactive oxygen species can be formed by fecapentaene-12 (FP-12). No specific conditions could be defined that resulted in the direct formation of oxygen radicals from FP-12. However, peroxidation of FP-12 by various peroxidative enzymes has been shown to result in the formation of superoxide adducts of the spin traps alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Addition of superoxide dismutase resulted in a decreased spectrum intensity, whereas the hydroxyl radical scavenger t-butyl alcohol (tBA) appeared of no influence on the signal, both confirming the formation of superoxide. The formation of hydroxyl radical spin adducts has been demonstrated after peroxidation of FP-12 in incubations with the spin-trapping agent 2,2,6,6-tetramethyl-piperidine (TMP). Further, the effects of scavenging hydroxyl radicals with respect to the genotoxic potential of FP-12 in the Salmonella mutagenicity assay has been investigated. It was clearly shown that radical scavenging reduced the number of revertants in Salmonella strains TA100, TA102 and TA104. This mutagenicity-reducing effect was more convincing using both spin traps DMPO and TMP as compared to the effect of hydroxyl radical scavengers tBA and DMSO. Based on these findings, a reaction scheme is proposed that suggests the formation of superoxide after peroxidation of FP-12, which is subsequently converted to hydroxyl radicals by the iron-catalysed Haber-Weiss reaction.
Carcinogenesis 1992 Jul
PMID:Electron spin resonance spectroscopy of oxygen radicals generated by synthetic fecapentaene-12 and reduction of fecapentaene mutagenicity to Salmonella typhimurium by hydroxyl radical scavenging. 132 51

Oxidative DNA damage is involved in mutagenesis, carcinogenesis, aging, radiation effects, and the action of several anticancer drugs. Accumulated evidence indicates that iron may play an important role in those processes. We studied the in vitro effect of low concentrations of Fe(II) alone or Fe(III) in the presence of reducing agents on supercoiled plasmid DNA. The assay, based on the relaxation and linearization of supercoiled DNA, is simple yet sensitive and quantitative. Iron mediated the production of single and double strand breaks in supercoiled DNA. Iron chelators, free radical scavengers, and enzymes of the oxygen reduction pathways modulated the DNA damage. Fe(III)-nitrilotriacetate (NTA) plus either H2O2, L-ascorbate, or L-cysteine produced single and double strand breaks as a function of reductant concentration. A combination of 0.1 microM Fe(III)-NTA and 100 microM L-ascorbate induced detectable DNA strand breaks after 30 min at 24 degrees C. Whereas superoxide dismutase was inhibitory only in systems containing H2O2 as reductant, catalase inhibited DNA breakage in all the iron-mediated systems studied. The effect of scavengers and enzymes indicates that H2O2 and .OH are involved in the DNA damaging process. These reactions may account for the toxicity and carcinogenicity associated with iron overload.
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PMID:Iron-mediated DNA damage: sensitive detection of DNA strand breakage catalyzed by iron. 143 83

Caloric restriction increases maximum achievable lifespan and offsets the time to development of degenerative disease. Part of these desirable effects may result from positive modulation of toxic events. We have shown that when rodents are placed on a diet that is reduced in total calories by 40%, several beneficial changes on biochemical systems which impact on toxicologic processes are positively enhanced. Lipid metabolism is reduced and, therefore, the potential for lipoperoxidation is reduced. Additionally, activity of enzymes that produce free radicals as byproducts (cytochrome P4502C11) are also reduced. Concurrently, we have shown that the "effective" activity of catalase and the activity of superoxide dismutase (which are required for the detoxification of toxic oxygen radicals) are significantly increased by caloric restriction. The activities of enzymes of drug and xenobiotic metabolism are also altered by caloric restriction. The effect upon activity may be to either decrease or increase activity, dependent upon whether the enzyme activates compounds to intermediates which may be more toxic or whether the enzyme acts to reduce toxicity. We have also shown that caloric restriction may affect the initiation stage of carcinogenesis. Aflatoxin B1 binding to hepatic nuclear DNA was reduced by caloric restriction (caloric restriction reduced both major adducts that are formed upon exposure to aflatoxin B1). caloric restriction also reduced cytochrome P4502C11 which converts aflatoxin B1 to its toxic epoxide, and may partly explain the reduction in binding. These results suggest that caloric restriction may, in part, extend the time to development of degenerative disease by altering basic biochemical mechanisms of toxicity.
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PMID:Modulation of chemical toxicity by modification of caloric intake. 144 3

Treatment of rats with a single carcinogenic dose of CdCl2 (i.e., 30 mumol/kg) caused severe hemorrhagic damage in the testis within the first 12 h after the metal. Subsequently, atrophy with calcification developed in the next 2-3 mo. Atrophied tissues regenerated during the 1 yr after exposure. Twelve hours after exposure to the Cd treatment, lipid peroxidation levels, Fe content, and cellular production of H2O2 were remarkably elevated in testicular Leydig cells, the target cell population for Cd carcinogenesis. At the same time, glutathione peroxidase activity rose, glutathione reductase and catalase activities were reduced, and superoxide dismutase activity was unchanged. Xanthine oxidase activity in Leydig cells was also elevated at 6 and 9 h after the Cd treatment. Reduced glutathione in testes was decreased and oxidized glutathione was increased 12 h after exposure to the metal. These facts suggest that the carcinogenic doses of Cd induced oxidative stress while compromising cellular defense mechanisms against such stress. Therefore, active oxygen species such as H2O2 may have an important role in the initiation of carcinogenesis within the target cell population.
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PMID:Role of oxidative stress in single-dose, cadmium-induced testicular cancer. 152 11

Active oxygen species derived from the interaction of potassium bromate (KBrO3), a rat renal carcinogen, with cells from rat kidney and other organs were examined by electron spin resonance spectrometry using the spin trapping agents 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and 2,2,6,6-tetramethylpiperidine (TEMP). DMPO-OH, an indicator of hydroxyl radical production, was generated from KBrO3 by kidney cells or homogenate, but not by liver preparations and to only a limited extent by heart and brain homogenates, suggesting relative kidney specificity. To assess what chemical components are responsible for production of DMPO-OH, several physiologically related materials were examined. Glucose, saccharose, albumin and methyl linolate were found not to be involved in the KBrO3 reaction, but reduced glutathione and also ferric ions participated to produce DMPO-OH. In addition, DMPO-OH production derived from the reaction of KBrO3 with kidney homogenate was not affected by superoxide dismutase, catalase or hydroxyl radical scavengers such as DMSO or ethanol, but was effectively inhibited by singlet oxygen scavengers such as histidine and NaN3, implying singlet oxygen production. To assess this possibility, TEMP was used as a trapping agent, and TEMPO, derived from singlet oxygen, was found to be produced by the reaction of KBrO3 with homogenates of kidney, but not of liver. Furthermore, singlet oxygen production was confirmed by studies of chemiluminescence using 2-methyl-6-phenyl-3,7-dihydroimidazo[1,2a]pyrazine-3-one. As a control, DMPO-OH was also demonstrated to be produced by a known singlet oxygen source, toluidine blue plus light. The results thus indicate that singlet oxygen is a very probably candidate for the active oxygen species generated in the specific interaction of KBrO3 with rat kidney cells in vitro. This raises the question of its concern with renal carcinogenicity in vivo.
Carcinogenesis 1992 Mar
PMID:Generation of active oxygen species in vitro by the interaction of potassium bromate with rat kidney cell. 154 21

The following species; superoxide (O2-.), hydrogen peroxide (H2O2), hydroxyl radical (.OH) and singlet oxygen (1O2), are generally called as reactive oxygen species (ROS). These species have been suggested to play important roles in various diseases caused by oxygen toxicity such as ischemia, carcinogenesis, inflammation, diabetes and aging. During the past two decades, considerable interests have been focused on chemical and biological research of ROS. We have also reported about the research results on ROS, which can be classified as following below; 1) chemical reactivities of O2-., 2) formation and toxicity of 1O2, 3) chemical reactivities of .OH, 4) enzyme mechanism of xanthine oxidase, 5) development of the compounds which induce the formation of O2-. and H2O2 in living cells and 6) development of superoxide dismutase mimics. These studies are reviewed from the standpoint of both chemical and biological interests.
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PMID:[Chemical and biochemical studies on reactivities, formations and toxicities of reactive oxygen species]. 164 54

Groups of rats, either dosed with N-nitrosodiethylamine (NDEA) for 10 weeks (from the age of 7 to 17 weeks) or untreated, were fed diets containing either 2% (low fat, LF) or 30% polyunsaturated fat (high fat, HF) on an equicaloric basis from 5 weeks until rats were 43 weeks old. Biochemical parameters were measured during and at the end of the experiment in various organs, blood, urine and exhaled air, for correlation with the presence or absence of tumors. The HF diet tended to increase the number of hepatic tumors induced by NDEA, while the number of extrahepatic tumors was higher in rats fed on the LF diet; also the overall tumor incidence was higher in the LF group. In the HF/NDEA group, only two benign extrahepatic tumors were found. Plasma total and free cholesterol and triglyceride concentrations were lower in the HF than the LF group without NDEA treatment. In animals bearing liver and/or extrahepatic tumors all plasma lipid concentrations were lower than in tumor-free animals. Only minor or no changes were detected in blood catalase activity, malondialdehyde level, reduced glutathione (GSH) level or GSH-related enzymes and excretion of thioethers in the urine due to dietary modulation or NDEA. Changes in the liver that were associated with the HF diet were: (i) increased amounts of some polyunsaturated fatty acids and of total phospholipids in liver microsomes; (ii) an enhanced level of lipid peroxidation in liver; (iii) a decrease in liver glutathione levels during NDEA treatment, with a simultaneous adaptive increase in superoxide dismutase levels, and a decrease in renal glutathione levels in both treated and untreated groups; (iv) enhanced microsomal induction of aminopyrine N-demethylase and epoxide hydrolase activities by NDEA, and (v) decreased hexose monophosphate shunt (HMS) activity. All mono-oxygenase activities were lower, and the activities of epoxide hydrolase, UDP-glucuronosyltransferase and HMS were higher, in liver tumors than in non-tumorous liver of similarly-treated rats. Neither diet nor NDEA had a major effect on drug-metabolizing enzyme activities in lung and kidney. HF diet significantly increased ethane exhalation (an indicator of the whole-body pro-oxidant state) over those on the LF diet: in rats on either diet, it was further increased when NDEA was given. Ethane exhalation was still elevated 30 weeks after the cessation of NDEA treatment. Our results suggest an association between the observed changes in biochemical parameters, notably oxidative stress, due to dietary modulation and the altered tumor incidence and organ distribution of tumors induced by NDEA.
Carcinogenesis 1991 Apr
PMID:Mechanisms of fat-related modulation of N-nitrosodiethylamine-induced tumors in rats: organ distribution, blood lipids, enzymes and pro-oxidant state. 167 40

Exposure of human keratinocytes to UVB irradiation resulted in formation of conjugated double bonds and thiobarbituric acid reactive material. The activities of superoxide dismutase and catalase, enzymes which protect cells against oxidative damage, were concomitantly reduced. The present study suggests that in keratinocytes, exposure to UVB irradiation leads to a chain of events resulting in lipid peroxidation reactions accompanied by an impairment of the cellular defence system against reactive oxygen species. These phenomena may act synergistically in UVB-induced cutaneous pathological processes, such as carcinogenesis.
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PMID:UVB irradiation induces lipid peroxidation and reduces antioxidant enzyme activities in human keratinocytes in vitro. 167 28


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