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)

Six large hepatic nodules obtained 46 to 74 weeks after a single dose of diethylnitrosamine (0.625 or 1.25 micrograms/gm) in infant C57BLxC3H F1 male mice were studied to elucidate the nature of intracytoplasmic inclusions in the hepatic cells of these nodules. By light microscopy, the nodules constituted a spectrum of lesions ranging from some which were well differentiated adenomas to others which were frank carcinomas. Round or oval eosinophilic intracytoplasmic inclusions were consistently seen in the well differentiated adenomatous lesions. Some of these inclusions were PAS positive and resisted diastase digestion while others were either negative or only weakly PAS positive. By electron microscopy, they were most commonly crystalline, contained a reticulated electron dense material and were located in the distended rough endoplasmic reticulum. On immunofluorescence the inclusions showed marked specific reactivity with antisera against human alpha-1-antitrypsin. The presence of alpha-1-antitrypsin in these inclusions was further supported by the resistance of these inclusions to digestion by trypsin or papain but not by the pepsin or pronase.
Carcinogenesis 1980 Jun
PMID:Alpha-1-antitrypsin in intracellular inclusions of diethylnitrosamine induced hepatomas of C57BLxC3H F1 mice. 626 19

Twenty-three cases of human hepatocellular carcinoma were examined electron microscopically, and intracytoplasmic deposits were detected and classified as follow: (1) inclusion bodies such as Mallory bodies, (2) fat droplets, (3) secondary lysosomal changes such as alpha- or beta-glycogen particle accumulations surrounded by a single membrane layer, myelin figure and lipofuscin granules, (4) abnormal changes in organellae such as alpha- or beta-glycogen particle accumulations, the hyperplasia of smooth endoplasmic reticulum, finger prints, glycogen bodies, larger peroxisomes and hypertrophy of bile canaliculus-like structures, (5) degenerative changes in cytoplasm evidenced by debris, focal cytoplasmic degradation and autophagic vacuoles. These intracytoplasmic deposits seem to play important roles in the pathogenesis of hepatocellular carcinoma, but the relation to carcinogenesis is still unclear.
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PMID:Ultrastructural study of intracytoplasmic deposits in human hepatocellular carcinoma. 632 43

Tumor promoters provoke the elaboration of oxygen radicals by direct chemical generation and through the indirect activation or alteration of cellular sources including membrane oxidases, peroxisomes, and electron transport chains in mitochondria and endoplasmic reticulum. Although direct measurement of amplified oxygen radical production in response to tumor promoters in target tissues remains problematic, studies with scavengers of reactive oxygen species demonstrate inhibition of biochemical and biological sequelae of tumor promoter exposure and provide strong presumptive evidence for oxygen radical involvement in this late stage of carcinogenesis. The critical macromolecular targets for these oxygen radicals remain undefined; however, they may include lipids, DNA, DNA repair systems, and other enzymes.
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PMID:Role of oxygen radicals in tumor promotion. 638 Oct 43

Young adult male Leeds strain rats were fed for up to 10 weeks on diets containing either 0.06% 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) or 0.06% 3'-MeDAB together with 0.0067% 3-methylcholanthrene (MeCh), which is known to inhibit the induction of hepatocarcinogenesis by the azo dye. Controls received either MeCh alone or a normal diet. Animals were killed at 10 days, 4 weeks and 10 weeks and their liver tissues examined by electron microscopy. Although MeCh did not prevent the induction of some non-specific fine structural changes such as glycogen depletion and proliferation of the smooth endoplasmic reticulum (ER), it did prevent the early dislocation and dispersal of the rough ER that was elicited by 3'-MeDAB. This provides further evidence indicating the importance to liver tumorigenesis of this rough ER change, which appears to be induced by all classes of chemical hepatocarcinogens and which, in comparative studies with carcinogen/non-carcinogen pairs of related chemicals, also appears to be specific to carcinogens.
Carcinogenesis 1983 Sep
PMID:Effects of inhibiting hepatocarcinogenesis upon the early fine structural changes induced in rat hepatocytes by 3'-methyl-4-dimethylaminoazobenzene. 641 76

The kinetics of cytochrome P-450 content in endoplasmic reticulum membranes at different stages of hepatocarcinogenesis was studied under the influence of unsaturated fatty acids by the EPR method. At early stages of carcinogenesis the preparations containing oleic, linoleic and arachidonic acids prevent changes in the cytochrome P-450 content usually observed in case of nitrosodiethylamine introduction. The diet containing unsaturated fatty acids has a stabilizing effect revealed by the similar changes in the content of cytochrome P-450, phosphatidyl choline and fatty acids composition and also in the level of organization of the endoplasmic reticulum membrane lipid bilayer.
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PMID:[Effect of modification of the lipid bilayer on the functioning of the electron transport chain of endoplasmic reticulum membranes in nitrosodiethylamine-induced hepatic carcinogenesis]. 652 77

Liver preparations from Syrian golden hamsters catalyze the metabolism of the pancreatic carcinogen N-nitroso-2,6-dimethylmorpholine largely to N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP). This reaction is catalyzed by a mixed-function oxidase in the presence of reduced nicotinamide adenine dinucleotide phosphate and oxygen at a rate of 3.8 nmol/min/mg of protein, and it is inhibited by known cytochrome P-450-specific inhibitors. A second potent pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) is converted to HPOP by hamster liver in which two enzyme systems appear to be involved. The first is a reductase associated with microsomes which reduces BOP to HPOP in the presence of reduced nicotinamide adenine dinucleotide at a rate of 9.1 nmol/min/mg of protein. The second enzyme is a cytosolic one which catalyzes the same reaction at a slower rate (2.3 nmol/min/mg of protein) and is more effective with reduced nicotinamide adenine dinucleotide phosphate as cofactor. Based on the amount of protein in hepatic cytosol and endoplasmic reticulum, the two enzymes may be involved to a similar extent in the reduction of BOP to HPOP in the liver. Pancreas, on the other hand, lacks the microsomal reductase for BOP but contains a cytosolic enzyme which catalyzes its reduction in the presence of reduced nicotinamide adenine dinucleotide phosphate at a rate of 0.35 nmol/min/mg of protein. Since both pancreatic carcinogens N-nitroso-2,6-dimethylmorpholine and BOP are metabolized to HPOP in the liver at rates much higher than those observed in the target organ pancreas, it is suggested that the liver may play an important role in pancreatic carcinogenesis in the hamster by these compounds.
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PMID:Metabolism of pancreatic carcinogens N-nitroso-2,6-dimethylmorpholine and N-nitrosobis(2-oxopropyl)amine by microsomes and cytosol of hamster pancreas and liver. 664 May 29

Morphometric data of normal and neoplastic urinary bladder epithelia have been collected from the Fischer rat FANFT model. Sequential measurements of volumes, surface areas, and numerical densities of organelles, and where pertinent, cellular compartments have been made during FANFT carcinogenesis, utilizing standard point and intersection counting methods. The data show that neoplastic transformation of rat bladder epithelium, and progression of FANFT tumors are associated with increasing volume densities of cells, nuclei, microvilli, rough endoplasmic reticulum, and mitochondria, as well as with decreasing volume densities of the cytoplasmic matrix, fusiform vesicles, Golgi complex, and lysosomes. Surface densities of the plasma membrane (microvillar), nuclei, rough endoplasmic reticulum, as well as mitochondrial outer and inner membranes progressively increase while surface densities of non-microvillar plasma membrane, fusiform vesicles, and Golgi complex decrease with time. Smooth endoplasmic reticulum reaches its maximum volume and surface densities in tumors present 26 weeks after the initiation of FANFT feedings (26-F tumors). This may reflect the function of smooth endoplasmic reticulum as the site of detoxification of the carcinogen, noting that FANFT is metabolized by microsomal enzymes, and in this experiment is fed only for 26 weeks. The nuclear/cytoplasmic ratio is 1:4 in normal Fischer rat urothelium, 1:3 in 26-F and 43-F tumors, which are noninvasive, and 1:2 in 61-F, which are invasive tumors. The quantitative data correlate well with the changes in degree of differentiation of the tumors and with their biological behavior.
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PMID:Cellular changes in rat urinary bladder carcinomas induced by FANFT: a quantitative electron microscopic analysis. 683 70

The protein compositions of subcellular fractions prepared from untreated and 12-O-tetradecanoyl phorbol-13-acetate (TPA)-treated Krebs II ascites cells were examined by SDS-polyacrylamide gel electrophoresis. After 6 h of TPA treatment a 65,000 dalton protein in the nuclear associated endoplasmic reticulum showed a 240% increase when compared with the untreated control cells. The amount of this protein was similar in both untreated and TPA-treated cells up to 4 h of in vitro incubation. Though present in all other subcellular fractions, the amount of the 65,000 dalton protein was the same in both untreated and TPA-treated cells. Small changes were also observed in the amounts of other proteins in the nuclear associated endoplasmic reticulum in TPA-treated cells. The possibility was tested that the increased amount of the protein may have represented increased ornithine decarboxylase activity in response to TPA treatment. The time dependent appearance of the enzyme in untreated and TPA-treated cells, however, and the behaviour and subcellular localization of the 65,000 dalton protein ruled out the possibility that this protein and ornithine decarboxylase are one and the same molecule.
Carcinogenesis 1983
PMID:The specific appearance of a 65,000 dalton protein in the nuclear associated endoplasmic reticulum of Krebs II ascites cells early after treatment with the phorbol ester TPA. 687 36

Male Leeds strain rats were fed a diet containing 5.0% by weight of acetamide (AA), for up to 35 weeks, inducing a high incidence of hepatic cell neoplasms. The sequential morphological changes induced by AA in the hepatic parenchymal cells were studied by electron microscopy and were compared with those observed in foci of cellular alteration, neoplastic nodules and hepatocellular carcinomata. The observed fine structural changes including early glycogen depletion, dispersal and dislocation of the rough endoplasmic reticulum (ER), smooth ER proliferation and nuclear irregularity and nucleolar abnormalities. Glycogenosis developed in some cells during treatment and was characteristic of the 'clear cell' foci, as well as being common in the neoplasms. The most consistent alteration, observed in parenchymal cells and the cells of foci, nodules and carcinomas, was that involving the rough ER. This persisted after withdrawal of AA from the diet, whereas many other changes were transient, and may represent a change in differentiation associated with neoplastic induction.
Carcinogenesis 1983 Sep
PMID:An electron microscope study of hepatocellular changes in the rat during chronic treatment with acetamide. Parenchyma, foci and neoplasms. 688 35

Changes in enzyme activity due to induction by chemicals is an important property that can determine the type of response seen in tissues exposed to environmental chemicals. Two major types of response, acute irreversible liver cell injury or death (necrosis) and long-term cancer induction, are discussed in terms of their modulation by enzyme induction. Most commonly, enzyme induction leads to a more severe toxic response by the liver, and to more cell death. However, inducers may have a protective effect, especially in carcinogenesis, when they most frequently protect against cancer induction if used early in the process. There is a discrepancy between this observation and the increase in mutagenic activity of liver preparations observed after induction. However, when enzyme induction occurs at a later stage, after initiation, it often accelerates or promotes cancer induction. Also, new cell populations constantly observed during liver carcinogenesis are composed of very hypertrophic hepatocytes containing a large amount of smooth endoplasmic reticulum. This is associated with a radical change in enzyme activities in the reticulum, which may account in part for the characteristic resistance exhibited by initiated cells to hepatotoxins and carcinogens. The resistance is considered to be an important property that may play a key role in the development of cancer under some circumstances.
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PMID:Toxicological significance of liver hypertrophy produced by inducers of drug-metabolizing enzymes. 690 64


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