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

The relative ability of arylacetamide deacetylase enzyme systems of dog liver to carry out the deacetylation of the carcinogens, 4-acetylaminobiphenyl, 2-acetylaminofluorene, and 2-acetylaminaphthalene, was examined. The arylacetamides were incubated with unfortified dog liver microsomes, and enzyme activity (nmol arylamine/mg protein/hr) was estimated by colorimetric quantitation of the resulting arylamines. The dog liver enzyme system displayed characteristics similar to those described for the rodent liver enzyme system in that enzyme activity was greatest in liver tissue, was localized in the microsomal subcellular fraction, required no cofactors, and was inhibited by heat, sodium fluoride, and thiol reagents. In five replicate assays, the relative rates of deacetylation were about 10, 6, and 1 with 4-acetylaminobiphenyl (84.8 +/- 12.4), 2-acetylaminofluorene (52.5 +/- 5.1), and 2-acetylaminonaphthalene (8.8 +/- 3.3), respectively. As a canine urinary bladder carcinogen, 4-acetylaminobiphenyl is considered more potent than 2-acetylaminofluroene, while 2-acetylaminonaphthalene is devoid of detectable carcinogenic activity, despite the fact that 2-aminoaphthalene is a well-established canine urinary bladder carcinogen. Removal of the acetyl group may be a requirement for urinary bladder carcinogenesis; accordingly, the present studies demonstrate the appearance of a direct relationship between dog liver deacetylase enzyme specificity and urinary bladder susceptibility to these carcinogenic arylacetamides.
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PMID:Enzymic deacetylation of carcinogenic arylacetamides by tissue microsomes of the dog and other species. 0 50

Glycolysis is not of importance for the process of carcinogenesis. It is very likely, however, that certain molecular-biological and genetic changes are produced which enable the malignant cell to develop an intensive glycolysis, for instance, to form specialized glycolytic isoenzymes already during oncogenesis, and may possible become effective in the primary tumour. As soon as the capacity of the cancer cell to intensive aerobic and anaerobic glycolysis has become manifest, this process is an irreversible one. The extent of glycolysis of a malignoma is greatly dependent on the degree of its dedifferentiation and vascularization (glucose supply), although a direct correlation between growth and the amount of lactic acid formed does not seem to exist. However, a certain utilization of glucose is essential for cell proliferation (supply of basic substances). In many cases there is a correlation between the extent of glycolysis measurable under optimal conditions in vitro (glycolytic power) in a malignant tumour and its growth rate recognizable in vivo. The formation of a strong capacity for glucose degradation via the Embden-Meyerhof pathway that cannot be fully utilized by the whole tumour in vivo is first of all designed to ensure survival and proliferation of cells even at extremely low levels of glucose supply. This process can be regarded as an adaptation of cancer cells to a situation of unsufficient supply. This circumstance endows the cancer cell with an essential advantage over the normal cell which enables or even promotes its invasive and destructive growth and metastatic dissemination. In this respect they differ, for instance, from benignant neoplasms. The possibility is discussed to control neoplastic growth by adjusting an optimal pH difference between normal and tumour tissue by combined administration of detoxicated drugs which are converted to their toxic forms only in the tumour by means of strongly pH-dependent exogenous enzymes.
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PMID:[Origination and importance of glycolysis for malignomas and utilization of this property in the chemotherapy of cancer (author's transl)]. 0 18

Hormones have widely different effects depending on species, dosage use, timing of dosage, route of administration, status of animals (re: pregnancy, stage of estrous cycle, age), and end point being measured. Hormones are essential to both maintenance and quality of life, and they occur in our environment with regularity. Hormones are seen by some persons as a regulatory dilemma because, when characterized under conditions of marked overdosage, the biological consequences are often undesirable. Because many of the naturally occurring hormones were identified long ago and have been studied for many decades, the reality is that much more knowledge is available on hormones than on more recently discovered substances, either naturally occurring or synthetic. The effects of hormones on tumors, either increases or decreases in incidence, appear to be indirect through alterations of normal physiological processes. The mechanism of action of hormones at the cellular level suggests that hormones are not involved in cancer by causing DNA changes, but in the degree of expression of changes in DNA that have occurred by other means. Key studies, especially at the molecular level, to further define the involvement of hormones in carcinogenesis should help us to define tolerance levels and aid with the regulatory dilemma.
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PMID:Reflections on Second Annual NCTR Hormone Research Symposium. 1 53

Cancer can be induced by radiation in any tissue where cancer occurs naturally. The observation that antenatal diagnostic radiography causes a small but definit increas in childhood cancer is as good evidence as could be expected in support of the scientific expectation that there would be no threshold of dose for carcinogenesis. A linear relation between radiation dose and frequency of of induced cancer is a necessary assumption for a system of radiological protection but is not necessarily a reasonable basis for realistic assessments of cancer risk. Indeed there are radiobiological and epidemiological reasons to the contrary. If the linear hypothesis is accepted then at the present time in the UK the routine practice of medicine is of about 2 orders of magnitude more important in causing cancer than environmental pollution by discharge of radio-activity. The acceptability of radiation safety standards for occupational exposure may be justified by comparison of radiation cancer risks with risks from fatal accidents in the safer industries. The acceptability of the corresponding standards for members of the public seems to require more public discussion of the concept of negligible risk. Emotional reactions to uncontrolled releases of radio-activity are based at least in part on a failure to appreciate the hypothesis of linearity.
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PMID:Radiation cancer, safety standards and current levels of exposure. 1 80

Environmental rather than genetic factors appear to be responsible for the causation of cancers involving epithelial surfaces, especially oropharyngeal cancers, cancers of the gastro-intestinal tract, cancers of the liver and gall-bladder, cancers of the cervix uteri and lung cancers. Epithelial surfaces which have mucus-bearing cells are particularly prone, because if these mucus cells are surrounded by an alkaline milieu over a prolonged period, the mucous of the epithelial cells is rendered fluid and is removed from the cells, of which it forms an integral part. This leads to proliferative changes with metaplasia, cell-atypia and a very significant increase in mitotic activity. Such changes are a prelude to carcinogenesis. In the case of many oropharyngeal cancers in Asia and Africa it is the alkaline slaked lime in the betel quid which is responsible; in the case of gastric cancers it is the reflux of the alkaline duodenal contents into the stomach; in the case of colon it is the absence of roughage, cellulose and vegetable fibres from the diet; in the case of the cervix uteri it is the frequency of coitus which gives rise to a highly alkaline seminal fluid; and in the case of cancer lung it is the alkaline cigarette smoke.
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PMID:New approaches to the causation and prevention of cancers of epithelial surfaces. 1 56

The effect of norepinephine, an adrenomietic drug, and of pyrroxane, its antagonist, on diethylnitrosoamine (DENA) hepatocarcinogenesis was studied in albino rats. Norepinephrine was found to stimulate carcinogenesis, whereas pyrroxane--to inhibit this process; the latter drug decreased the incidence of multicentric tumours of the liver. In vitro experiments on the isolated rat atria showed low DENA concentrations (1x10(-6) to 1x10(-8) M) to sensitize the atrium adrenoreceptors to the endogenous and exogenous norepinephrine. A new hypothesis on the adrenergic component in the DENA carcinogenic effect caused by the endogenous norepinephrine is presented.
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PMID:[Adrenergic component in the hepatotropic, carcinogenic effect of diethylnitrosamine]. 1 87

In these experiments, we tested in various in vivo assays the immune responses of inbred C3H/HeN(MTV-) (C3H-) mice during carcinogenesis by chronic exposure to UV irradiation. Although the UV-treated mice were unable to reject syngeneic UV-induced tumor transplants, they rejected H-2-incompatible tumor allografts and H-2-compatible skin allografts. The primary hemagglutinin response to sheep red blood cells was normal in these mice, as were the induction of a local graft-versus-host reaction with lymphoid cells from UV-irradiated donors and the induction of an inflammatory response to dimethyl sulfoxide in the footpads of UV-treated mice. An early transient depression of two reactions in UV-irradiated mice occurred: delayed hypersensitivity to dinitrochlorobenzene measured by footpad swelling and the graft-versus-host reaction in UV-irradiated recipients measured by the use of the popliteal lymph node weight gain assay. Both of these reactions returned to a normal level before the development of primary tumors. We conclude that the inability of UV-irradiated mice to reject syngeneic and autochthonous UV-induced tumors was not due to a generalized immunosuppressive effect of chronic UV irradiation.
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PMID:In vivo immune responses of mice during carcinogenesis by ultraviolet irradiation. 2 May 14

N-nitrosomorpholine (NM)-induced pulmonary carcinogenesis was examined by light and electron microscopy in a 20-week serial sacrifice study using Syrian golden hamsters. First to be observed were a proliferation of endocrine APUD cells and a formation of lamellated inclusion bodies in the cytoplasm of Clara cells. After continued NM treatment, APUD cells underwent squamous metaplasia and Clara cells invaded the pulmonary tissues adjacent to the bronchi. Lung tumors consisted of cells possessing numerous lamellated inclusion bodies in their cytoplasm and a few squamous metaplastic and APUD cells. The observed pathologic alterations closely resembled those found after treatment with N-diethylnitrosamine (DEN) and N-dibutylnitrosamine (DBN) but were completely different from the cellular reactions induced by polycyclic aromatic hydrocarbons. It is concluded that the observed alterations of APUD cells and Clara cells are specific to nitrosamines.
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PMID:Sequential morphologic alterations in the bronchial epithelium of Syrian golden hamsters during N-nitrosomorpholine-induced pulmonary tumorigenesis. 2 Jul 81

The stages of initiation and promotion in the natural history of epidermal carcinogenesis have been known for many years. Recently, experimental systems other than skin have been shown to exhibit similar, if not completely analogous, stages in the natural history of neoplasia. In particular, the demonstration by Peraino and his associates that phenobarbital may enhance the production of hepatomas by a relatively subcarcinogenic dose of acetylaminofluorene was one of the first demonstrations of stages occurring in an extraepidermal neoplasm. Studies reported in this paper have demonstrated that administration of phenobarbital (0.05% in the diet) for 6 months following a single dose of diethylnitrosamine (5 to 10 mg/kg) given within 24 hours after partial hepatectomy resulted in a marked increase in the number of enzyme-altered foci in the liver as well as in the production of hepatocellular carcinomas. This was compared to animals receiving only a single dose of diethylnitrosamine following partial hepatectomy with no further treatment, in which only a relatively small number of foci were evident in the absence of phenobarbital feeding. Using three different enzyme markers, a distinct degree of phenotypic heterogeneity of the enzyme-altered foci in liver was demonstrated. These studies have shown that liver carcinogensis can be readily divided into two stages: a) initiation by a single dose of diethylnitrosamine following partial hepatectomy and b) promotion by the continuous feeding of phenobarbital. Furthermore, the immediate progeny of the initiated cells, the enzyme-altered focus, may be recognized by suitable microscopic means prior to the formation of gross lesions as required in the skin system. These initiated cell populations exhibit a degree of biochemical heterogeneity which reflects that seen in fully developed hepatic neoplasms, suggesting that promotion and progression in this system does not significantly alter the basic biochemical characteristics of the initiated cell.
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PMID:The natural history of neoplasia. Newer insights into an old problem. 2 65

The effect of a number of neurotropic drugs on diethylnitrosoamine (DENA)-induced chemical carcinogenesis was studied by applying pharmacological, morphological and biochemical techniques. Atropine stimulated significantly the rat liver and esophagus carcinogenesis, whereas the alpha-adrenoblocking agent, a pyrrhoxane analogue, and, particularly, proserine inhibited these processes. All animals treated with DENA demonstrated a significant increase of liver mitochondrial monoaminoxidase activity. These findings as well as the evidence of a stimulating effect of exogenous norepinephrine on carcionogenesis, together with the literature sources on carcinogenic and modifying carcinogenesis action of neurotropics allow the authors to formulate a concet of the trigger role played by catecholamines in the DENA-induced cell transformation and carcinogenesis.
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PMID:[Possible neuropharmacological regulation of chemical carcinogenesis caused by diethylnitrosamine]. 2 98


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