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

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

The carcinogen N-hydroxy-1-naphthylamine reacted with nucleic acids and protein under slightly acidic conditions (pH 5) to form covalently bound derivatives with 3 to 20 naphthyl residues/1000 monomer units. The level of binding was in the following order: DNA greater than polyguanylic acid greater than denatured DNA and ribosomal RNA greater than serum albumin greater than transfer RNA greater than polyadenylic acid. Reactions with nucleosides and nucleotides were not detected, and the binding of N-hydroxy-1-naphthylamine to DNA was not inhibited by the addition of nucleosides, nucleotides, methionine, or glutathione. The reaction rates were first order with respect to both DNA and N-hydroxy-1-naphthylamine concentrations. Enzymatic hydrolysis of the DNA containing naphthyl residues yielded 3 nucleoside-arylamine adducts. The major adduct was identified by chemical, ultraviolet, nuclear magnetic resonance, and mass spectrometric analyses as N-(deoxyguanosin-O6-yl)-1-naphthylamine. The other two adducts were identified as 2-(deoxyguanosin-O6-yl)-1-naphthylamine and its decomposition product. Direct evidence for acid-dependent arylnitrenium ion formation was obtained by isotope exchange upon solvolysis of N-hydroxy-1-naphthylamine in acidic H2 18O, and carbocation formation was indicated by the formation of the solvolysis products, 1-amino-2-naphthol and 1-amino-4-naphthol. These studies demonstrated the conversion of a carcinogenic N-hydroxy arylamine to electrophilic arylnitrenium ion and carbocation species that display high selectivity toward macromolecules. The roles of these electrophiles and their macromolecular adducts in the initiation of urinary bladder carcinogenesis through formation of promutagenic lesions in DNA are suggested.
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PMID:Guanyl O6-arylamination and O6-arylation of DNA by the carcinogen N-hydroxy-1-naphthylamine. 2 2

The chemical carcinogen hydrazine is a potent stimulator of guanylate cyclase. In the present investigation we found that three chemical carcinogens structurally related to hydrazine, isonicotinic acid hydrazide, hydrazine sulfate, and dimethylhydrazine, decreased guanylate cyclase activity. It is of interest that hydrazine has been shown to increase DNA synthesis whereas isonicotinic acid hydrazide, hydrazine sulfate, and dimethylhydrazine decrease DNA synthesis. The relationship, if any, linking the guanylate cyclase-cyclic GMP system to DNA synthesis and carcinogenesis remains to be explored.
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PMID:Effect of hydrazine, isonicotinic acid hydrazide, hydrazine sulfate, and dimethylhydrazine on guanylate cyclase activity. 3 Jun 19

To estimate the influence of topical treatment with DMBA and induced tumors on delayed hypersensitivity, the response of spleen lymphocytes to PHA in vitro and macrophage migration inhibition with PHA were studied in DMBA-treated hairless mice. DNA synthesis and blastic transformation of cultured lymphocytes decreased after 6-12 weeks of DMBA application. Lymphocyte response to PHA gradually diminished during the experiment, as compared with control animals. Since the malignant transformation of skin tumors was not observed before 16 weeks of DMBA carcinogenesis, it seems that derangements in cellular immunity preceded the malignant proliferation. The increase in spleen weight and the absence of PHA-induced inhibition of macrophage migration in hairless mice with malignant tumors may also be related to the influence of the tumor itself on the lymphatic system of experimental animals.
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PMID:Immunological phenomena in harmless mice during experimental carcinogenesis induced with long-term topical application of 7, 12-dimethylbenzanthracene (DMBA). 4 67

The human uterine cervix offers a unique opportunity to study the early lesions of squamous cell carcinoma, i.e., carcinoma in situ and dysplasia [combined as cervical intraepithelial neoplasia (CIN)]. In vivo, the patients with CIN have the epidemiological common denominators or "markers" of early onset of coitus, multiple sexual partners, 1st delivery before age 20, and antibodies to herpes simplex virus type 2 more frequently than do controls. The lesions themselves have specific epithelial and vascular changes observable with the colposcope in addition to the usual histological markers from biopsy specimens. The chromosomes and DNA content of cells in these lesions are abnormal. In vitro, the cells from CIN have characteristics somewhat between normal and invasive carcinoma. They lack contact inhibition and may be transferred for several generations, in contrast to normal cervical epithelial cells. The fibroblasts from areas adjacent to DIN are different from normal fibroblasts. The mitotic mechanism in cells cultured from CIN has a significantly prolonged prophase and telophase when compared to similar normal cells. The surface of CIN cells, unlike normal cells, has numerous microvilli when examined by scanning electron microscopy and has characteristic differences from normal cells with numerous elongated, irregular microvilli. With the transmission electron microscope, an increase in microvilli and a decrease in desmosomes and tonofibrils are seen in CIN cells. Some of these markers are being used clinically to manage patients with CIN. Other markers are the basis for further investigation of human carcinogenesis.
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PMID:In vivo and in vitro "markers" of human cervical intraepithelial neoplasia. 5 20

Changes of the cell cycle during carcinogenesis of hamster cheek pouch epithelium were studied and it was demonstrated that in hyperplastic and neoplastic stages, the cell cycle time decreased to approximately 2/3 and 1/3 of the normal control, respectively. A nominal growth fraction was found to exceed unity in carcinogen-treated epithelium, whether hyperplastic or neoplastic. This result seems to indicate that a considerable number of cells in which DNA synthesis is stimulated by the carcinogen fail to enter mitosis. A possible implication of repair synthesis is also discussed.
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PMID:Changes of the cell cycle during carcinogenesis of hamster cheek pouch epithelium by 7,12-dimethylbenz[a]anthracene. 9 14

Polychlorinated biphenyls (PCBs) are widespread environmental pollutants which have been shown to be carcinogenic. One possible mechanism for the apparent carcinogenicity of PCBs is their metabolism to phenolic metabolites through an arene oxide intermediate, with the arene oxide that is formed being the ultimate mutagenic or carcinogenic species. The ability of a tetrachlorobiphenyl and its phenolic and arene oxide metabolites to cause single strand breaks in DNA was therefore examined. 2,2',5,5'-TCB-3,4-epoxide was more potent in causing DNA single strand breaks than either 2,2',5,5'-TCB or a mixture of 3-hydroxy and 4-hydroxy-2,2',5,5'-TCB. These results support the idea that PCB epoxide may be involved in PCB carcinogenesis.
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PMID:DNA single strand breaks caused by 2,2',5,5'-tetrachlorobiphenyl and its metabolites. 11 26

Living organisms have various mechanisms for repairing spontaneous and mutagen-induced damage in DNA. Mutagenesis, teratogenesis, and carcinogenesis are discussed in relation to DNA misrepair. The existence of highly efficient genetic mechanisms for tolerating environmental threats is argued from evolutionary viewpoints.
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PMID:Evolutionary considerations of DNA repair in relation to mutagenesis, teratogenesis and carcinogenesis. 12 Nov 55

The damage and repair of rat brain DNA was studied in vivo after a single carcinogenic dose of ethylnitrosourea. Fragmentation of the brain DNA produced by this carcinogen was demonstrated on alkaline sucrose gradients. By the 24th hrs after treatment with ethylnitrosourea the single-strand damage to DNA was not completely repaired. As the highly differentiated cells of the central nervous system do not proliferate, it is possible that during brain carcinogenesis delayed repair of DNA of primitive cells might be needed for the formation of tumor anlage.
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PMID:Strand breakage in rat brain DNA and its repair induced by ethylnitrosourea in vivo. 12 17

The present report is a continuation of our previous studies on the biochemical mechanisms of carcinogenesis; studying the nature of interactions taking place between Ethylnitrosourea and DNA, RNA and protein of various stages of their synthetic activity. As a model system we chose partially hepatectomized mice live 36 hrs after surgery. Synthetic macromolecule activity in the remaining liver segment was determined by means of 3H-thymidine, 3H-uridine and 3H-leucine. We observed complete depression of DNA synthetic activity (immediately after Ethylnitrosourea administration it remained depressed almost through out the whole period of our observations) while protein synthetic activity was highly elevated. Qualitative changes of soluble proteins which were analyzed by isoelectric fractionation on 5% polyacrylamide after previous 3H- and 14C-leucine incorporation, could not be detected. Our biochemical data are correlated with histological studies and with the tumour incidence following the Ethylnitrosourea treatment of partially hepatectomized mice in the course of long-term experiments. The results provide guideline for further analysis, which should be modified according to the information concerning Ethylnitrosourea carcinogenesis induced 36 hours after partial hepatectmoy.
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PMID:Macromolecular synthetic activity in mice regenerating liver after ethylnitrosourea injection. 15 33


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