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

Analytical epidemiology techniques were used to study the malignant neoplasms prevalence in the population of Magnitogorsk (400,000), and among the workers engaged in the Magnitogorsk metallurgical plant (64,000 workers). Revealed was that the malignant neoplasms related morbidity rate was 1.6 higher in men and 3.2 higher in women among the plant workers as compared with the city population in general. The cancer risk factors were predominantly occupational ones, e. i. the major industrial carcinogens--benzopyrene in tars and carbon-black; benzol, chromium and nickel in the dust; the carcinogenesis modifying substances--nitrogen oxide, sulfur dioxide, phenols, iron oxides, lead and its non-organic compounds, high temperatures. The data received can be used in further studies and elaboration of primary preventive measures.
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PMID:[Comparative analysis of oncological morbidity in the population of an industrial city and workers of a metallurgical plant]. 186 76

The possibility that the interaction of C-nitroso aromatics with polyunsaturated fatty acids (PUFA) causes lipid peroxidation was investigated through determination of conjugated diene and malodialdehyde (MDA) formation after anaerobic/aerobic vs. aerobic incubations of nitrosobenzene (NOB) or 2-nitrosofluorene (2-NOF) with linoleic, linolenic or arachidonic acid or methyl linolenate. Anaerobic incubation of NOB or 2-NOF with linolenic acid at the molar ratio of 1:1 for 24 h yielded approximately 5.5-13% of the PUFA as conjugated diene which appeared stable upon exposure to air. Interaction of PUFA and 2-NOF or NOB yielded MDA, the amounts of which were significantly greater when 24-h anaerobic preceded 1-6-h aerobic incubation. Furthermore, the differences in the amounts of MDA resulting from 24- and 0-h anaerobic incubations were significantly greater when the molar ratio of 2-NOF (or NOB) to PUFA was increased (2.0 greater than 1.0 greater than 0.5). Superoxide dismutase or catalase had no effect on the yields of MDA following either anaerobic/aerobic or aerobic incubations of PUFA and 2-NOF. EDTA (1 or 10 microM) had no effect on the yields of MDA from aerobic incubations, but it decreased the amounts of MDA (by approximately 30 or 60%, respectively) from anaerobic/aerobic incubations. The data suggested that inhibition by EDTA was due to chelation of trace iron, which following anaerobic interaction of PUFA and 2-NOF might have been reduced to Fe2+ and contributed to the enhanced lipid peroxidation. Thus, adduction of C-nitroso aromatics to PUFA yields radical species which directly and/or via reaction with trace iron lead to lipid peroxidation. The lipophilicity of C-nitroso aromatics suggests that this process may be of consequence in their mutagenesis/carcinogenesis.
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PMID:Interaction of C-nitroso aromatics with polyunsaturated fatty acids: route to lipid peroxidation. 189 3

Since the 1960s, the loss of sulfomucin from colonic epithelium has been considered to be an indicator of an early stage of carcinogenesis; yet, the biochemical basis for this phenomenon has never been elucidated. We recently prepared a monoclonal antibody (mAb) 91.9H that immunoprecipitates the normal colonic mucins metabolically incorporating [35S]-sulfate. This mouse IgG1 antibody did not cross-react with colon carcinoma mucins that lack sulfate groups. Using normal colonic epithelia unlabeled or radiolabeled with [35S]sulfate and [3H]glucosamine, we purified a high molecular weight glycoprotein that reacts with mAb 91.9H. This was achieved by a combination of DEAE-cellulose anion-exchange chromatography, consecutive treatments with chondroitinase ABC plus heparitinase and with sodium dodecyl sulfate plus 2-mercaptoethanol, and gel filtration on Sepharose CL-2B in the presence of 8 M urea. Antibody reactivity was found in acidic but not neutral high molecular weight glycoproteins. After Sepharose CL-2B fractionation, the mAb 91.9H-reactive fractions consisted of a component with an approximate molecular weight of 500,000-900,000. A purified sulfomucin contained protein, neutral sugar, amino sugar, sialic acid, and sulfate in an approximate ratio of 2.5:1.0:1.1:0.4:0.5. The polypeptide portion was rich in hydrophilic amino acids, particularly threonine. Binding of mAb 91.9H in solid-phase assays was inhibited to 50% by purified normal colon acidic mucin at doses of 5-50 micrograms/ml, depending on different preparations. Various glycosaminoglycans or sulfatides did not show inhibitory activity. Sulfomucin reactivity with mAb 91.9H, as determined by solid-phase-binding inhibition and by dot blot assays, was significantly reduced by chemical desulfation of sulfomucins with anhydrous hydrochloric acid, suggesting that sulfate groups served as a portion of the immunochemical determinant for this antibody. Sulfate residues were apparently linked to alkaline-sensitive carbohydrate chains, but alkaline-released carbohydrate chains did not react with mAb 91.9H. Immunohistochemical examinations showed that mAb 91.9H bound normal colonic epithelial cells, which also stained with high-iron diamine, more strongly than it bound colon carcinoma cells.
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PMID:Human colonic sulfomucin identified by a specific monoclonal antibody. 191 91

The modulating effect of five dose levels of butylated hydroxytoluene (BHT) on liver and bladder carcinogenesis induced in rats by concurrent exposure to 2-acetylaminofluorene (AAF) was investigated. AAF at a low dose of 50 ppm was fed simultaneously with concentrations of 100, 300, 1000, 3000, or 6000 ppm BHT in the diet to male F344 rats for up to 76 weeks. By 12 weeks, AAF alone induced altered hepatocellular foci, identified by iron storage deficiency and gamma-glutamyltranspeptidase activity. At subsequent time points of 24, 36, and 48 weeks, the number of foci progressively increased, and at the end of the study, the incidence of liver neoplasms was 100%, a new finding with such a low dose of AAF. Simultaneous feeding of BHT inhibited the induction of liver altered foci by AAF in a dose-related manner and reduced the incidence of hepatocellular carcinomas and the number of liver neoplasms per animal. Feeding of 6000 ppm BHT, but not of lower doses, together with AAF resulted in an increase in the incidence and multiplicity of bladder neoplasms, and 3000 ppm increased nodular hyperplasia of the bladder. These results suggest that the chemoprevention by BHT of cancer resulting from low-level long-term carcinogen exposure may be achieved at doses that do not produce adverse effects.
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PMID:Modulation by butylated hydroxytoluene of liver and bladder carcinogenesis induced by chronic low-level exposure to 2-acetylaminofluorene. 193 82

The hypothesis that low body iron stores are protective against cancer whereas high body stores promote tumor occurrence was examined in the 1-methyl-1-nitrosourea (MNU)-induced experimental model for breast cancer. Twenty-one-day-old female Sprague-Dawley rats were randomized into one of three experimental groups and fed a formulation of AIN-76A diet modified to be low in iron (2 p.p.m.), or the same diet supplemented with an adequate (120 p.p.m.) or excess (1200 p.p.m.) amount of iron provided as FeSO4.7H2O. Rats were maintained on their respective diets throughout the experiment which was terminated 32 weeks post carcinogen administration. Rats were injected i.p. with either 25 mg MNU/kg body wt or the saline-solvent in which MNU was dissolved at 50 days of age. In the first 14 weeks, dietary iron deficiency resulted in a low hematocrit and a decrease in weight gain. The appearance of mammary tumors was markedly suppressed in this group compared to those given an adequate or excess level of iron. It has been reported in the literature that reduction in weight gain due to food restriction at a period immediately after carcinogen administration severely inhibits the subsequent development of tumors. Thus the low tumor incidence in the iron-deficient rats during this time frame could be attributed to the combined effects of low hematocrit and depressed weight gain. For the period between week 14 and week 32, the hematocrit in the iron-deficient animals was maintained at a normal level, and the body wt of these rats was comparable to that of the controls given an adequate level of iron. The rate of tumor appearance in the iron-deficient group during the second half of the experiment was similar to that of the iron-adequate group in the first half of the experiment. In other words, it appeared that once hematocrit and body wt gain were restored to normal in the iron-deficient animals, tumor incidence was only minimally affected by low dietary iron. In the second half of the experiment, the tumor incidence in the adequate iron group seemed to have plateaued, whereas it continued to rise in the excess iron group. Thus excess iron appears to be more prominent than iron deficiency in modification of mammary carcinogenesis, especially when the confounding effects of low hematocrit and reduced weight gain are taken into consideration in the latter case.
Carcinogenesis 1991 Jan
PMID:Effect of dietary iron deficiency or excess on the induction of mammary carcinogenesis by 1-methyl-1-nitrosourea. 198 69

Feeding mice diets containing different amounts of Fe-fumarate over a period of 4 weeks resulted in a dose-dependent increase of iron concentrations in liver as well as proximal and distal colon. In parallel, a dose-dependent increase in lipid peroxidation was observed in these organs; both effects were well correlated. No significant effects were seen in other organs (lung, heart, brain or kidney). As dietary iron was shown to enhance dimethylhydrazine-induced colon carcinogenesis in mice, it is concluded that oxygen activation and lipid peroxidation might be involved in colon tumorigenesis and cell proliferation.
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PMID:Enhancement by dietary iron of lipid peroxidation in mouse colon. 209 12

The level of quinone oxidoreductases (microsomal and cytosolic DT-diaphorase, NADPH-cytochrome P450 reductase and NADH-cytochrome b5 reductase), superoxide dismutase and glutathione-related enzymatic activities in diethylstilbestrol (DES)-induced carcinogenesis in kidney from Syrian golden hamsters are presented. Animals that exhibited two different stages of DES-induced carcinogenesis in kidney--pre- and neoplastic lesions and tumorous lesions (after 6 and 8 months of continuous exposure to DES respectively)--were studied in comparison to kidneys from control animals. A dramatic decrease in microsomal and cytosolic DT-diaphorase activities (13.6 and 37.8% of controls), as well as in glutathione disulphide reductase (39.5%), and less marked in superoxide dismutase (45.6%), NADH cytochrome b5 reductase (61.9%) glutathione transferase (GST) towards 1-chloro-2,4-dinitrobenzene (CDNB) (66.2%) and glutathione peroxidase (GSH-Px) (80%) activities, were observed in kidneys with pre- and neoplastic lesions. NADPH-cytochrome P450 reductase and GST activity towards 4-hydroxy-2,3-trans-nonenal (4-HNE) showed no statistically significant variation at this stage of carcinogenesis. In kidney from animals with tumorous lesions, all the enzymatic activities mentioned above decreased, except for superoxide dismutase, which was increased to 186% of the control activity. GST activity towards 4-HNE again showed no statistically significant variation. These results suggest that if one-electron reduction of diethylstilbestrol-4',4''-quinone (DESQ) occurs, it may play a very important role in the development of DES carcinogenesis (pre- and neoplastic lesions), since at this stage of carcinogenesis the primary defense mechanisms against the oxygen free radicals generated in this way, i.e. SOD activity, is reduced to less than a half of control values. Both cytosolic and microsomal DT-diaphorase activities are unable at this stage of carcinogenesis to promote effectively the two-electron reduction of DESQ, which would avoid the initial formation of superoxide anion. The consequences of these decreases may be an increased steady-state concentration of superoxide anion and hydrogen peroxide, which in the presence of iron might lead to lipid peroxidation. GST activity towards 4-HNE could be responsible for the possible higher steady-state concentration of this lipid peroxidation product during DES treatment. The induction of DT-diaphorase and its protective role in the prevention of the development of pre- and neoplastic lesions in kidney from Syrian golden hamster during DES treatment is also discussed.
Carcinogenesis 1990 Oct
PMID:The levels of quinone reductases, superoxide dismutase and glutathione-related enzymatic activities in diethylstilbestrol-induced carcinogenesis in the kidney of male Syrian golden hamsters. 211 5

Among several recently developed analytical methods, 32P-postlabeling analysis is a highly sensitive method for the detection and measurement of covalent carcinogen-DNA adducts and other DNA modifications. Since the method does not require radioactive carcinogens, it is suitable for DNA of humans exposed to environmental or occupational genotoxicants. The basic procedure entails the enzymatic incorporation of 32P-label into monomeric or dimeric hydrolysis products of DNA, followed by chromatographic mapping and autoradiography of the 32P-labeled digestion products and quantitation by scintillation spectrometry. Microgram amounts of DNA are analyzed; thus the assay is well suited for limited amounts of cells or tissue. Various versions of the assay afford different sensitivities of adduct detection. Under optimal conditions, one aromatic or bulky/hydrophobic adduct in 10(8)-10(10) nucleotides can be detected and measured (corresponding to 0.3-30 amol adduct/microgram DNA or 0.1-10 nmol adduct/mol DNA-P). The assay has been successfully applied to a variety of mutagenic (genotoxic) as well as non-mutagenic carcinogens. In humans, the 32P-postlabeling assay has been applied to DNA specimens from cigarette smokers, iron foundry workers, and coke oven workers. Estimation of total aromatic adduct levels in exposed individuals gave values of 1 adduct in 10(6)-10(8) DNA nucleotides. These values are similar to the total levels of persistent adducts in tissues of animals after exposure to initiating or carcinogenic doses of authentic aromatic genotoxicants. Among the non-mutagenic carcinogens investigated are estrogens, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), choline-devoid diet, carbon tetrachloride, and peroxisome proliferators. In addition, age-dependent DNA modifications (I-compounds) are being detected by 32P-postlabeling in animals that have not been knowingly exposed to mutagens/carcinogens. I-compound profiles and levels are dependent on species, tissue, sex, and diet. Reduced levels of I-compounds have been consistently noted in the target organ of carcinogen-exposed animals and in resulting neoplasms, suggesting that I-compound loss may play a role in carcinogenesis.
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PMID:Monitoring carcinogen actions on DNA by 32P-postlabeling. 213 85

Male Ah-responsive C57BL/10ScSn mice received a single dose of iron-dextran (600 mg Fe/kg) and were fed a diet containing 0.01% of the PCBs mixture Aroclor 1254 for up to 12 months. Iron caused a marked synergistic increase in liver size from 2 months with greatly elevated mitotic rates, numbers of basophilic foci and incidences of bile duct and oval cell proliferation. Although at 4 months much of the liver enlargement was due to iron-depleted hyperplastic regions and lipid accumulation, by 8 months seven out of nine mice had nodules (hepatocellular adenomas) whereas none were observed in the Aroclor alone group. After 12 months, 16 out of 18 mice had multiple nodules and/or hepatocellular carcinomas whereas only one of 16 mice was positive in a group not given iron. Basophilic nodules were more common than clear cell nodules in those mice with carcinomas than in those animals without. Preloading with iron also greatly enhanced the development of cholangiofibrosis at 8 and 12 months. Preliminary experiments with the polybrominated biphenyl mixture Firemaster BP-6 indicated a similar synergistic interaction with iron. No effects of iron and Aroclor 1254 on the liver were observed in the Ah-nonresponsive strain DBA/2. Iron potentiated the development of uroporphyria after exposure to those chemicals in C57BL/10ScSn mice but not in the DBA/2 mice. Therefore in C57BL/10ScSn mice the carcinogenicity of PCBs and possibly PBBs, is modulated by iron status and probably not at a late stage where these chemicals may act in a promotional manner.
Carcinogenesis 1990 Mar
PMID:Iron as a synergist for hepatocellular carcinoma induced by polychlorinated biphenyls in Ah-responsive C57BL/10ScSn mice. 215 20

The induction of heme oxygenase by both hydrogen peroxide and UVA (365 nm) radiation in normal human skin fibroblasts is prevented by prior treatment of cells with the specific iron chelators, o-phenanthroline or desferrioxamine. In addition, both iron chelators protected cells against the lethal effects of H2O2 treatment or UVA irradiation. We propose that the generation of the highly reactive hydroxyl radical by an iron catalyzed Fenton reaction is involved both in the induction of this stress response and, at least in part, in cell killing by the two treatments. These results are also consistent with the idea that the heme oxygenase gene is induced in response to oxidative stress and that its induction may constitute an inducible protective mechanism against oxidative damage induced by both hydrogen peroxide and UVA radiation.
Carcinogenesis 1990 May
PMID:Induction of the heme oxygenase gene in human skin fibroblasts by hydrogen peroxide and UVA (365 nm) radiation: evidence for the involvement of the hydroxyl radical. 215 88


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