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Carcinogenesis induced by low-dose radiation

harder to repair than single DSBs and SSBs. 11 Density of radiation correlates with reparability of DNA lesions, with densely ionizing radiation being harder to repair. Radiation stimulates DNA damage repair through non-homologous end-joining (NEHJ) 12 , an error prone pathway that can lead to induction of chromosome aberrations, which in turn may cause genomic instability. 13 Genomic instability has been connected to induction of most of the human cancers, however currently the exact mechanism of radiation-induced carcinogenesis is not clear. The dose-rate of

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Polyamines and carcinogenesis


The naturally occurring polyamines, spermine, spermidine and the diamine putrescine are widespread in nature. They have been implicated in growth and differentiation processes. In 1967, we reported that cancer cells are rich in polyamines. Subsequently, it has been shown that polyamines are released from cancer cells and may be detected in body fluids such as urine, blood and cerebrospinal fluids. It has also been demonstrated that the increase in cellular polyamine levels is an early and an obligatory event in the process of malignant transformation. This increase in cellular polyamine concentration is due to the activation of ornithine decarboxylase (ODC), which catalyses the rate limiting step in polyamine synthesis by converting ornithine to putrescine. Assays of urinary and blood polyamines have been used to detect cancer and to determine the success of therapy. A sensitive, rapid, chemiluminescence-based method for the determination of diamines and polyamines was developed and 2.000 urine samples were tested. An interesting "gene therapy" system for injecting amine oxidases into normal and transformed cells was developed as follows: serum amine oxidase and porcine kidney damine oxidase were trapped within reconstituted Sendai virus envelopes. Chick or rat fibroblasts, transformed by Rous sarcoma virus, were more susceptible to the injected enzymes, compared to the normal culture, when macromolecular synthesis was tested. An in vitro chemosensitivity assay for the testing of the sensitivity of cancer cells from individual patients ("tailored treatment") was also developed. All these studies stress the importance of polyamines in carcinogenesis.

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DNA methylation: gene expression regulation

References Auerkari, E.I. 2006. Methylation of tumor suppressor genes p16(INK4a), p27(Kip1) and E-cadherin in carcinogenesis. Oral Oncology, 42(1): 5–13. Brait, M. & Sidransky, D. 2011. Cancer epigenetics: above and beyond. Toxicology Mechanisms and Methods, 21(4): 275–288. Carone, B.R., Fauquier, L., Habib, N., Shea, J.M., Hart, C.E., Li, R., Bock, C., Li, C., Gu, H., Zamore, P.D., Meissner, A., Weng, Z., Hofmann, H.A., Friedman, N. & Rando, O.J. 2010. Paternally induced transgenerational environmental reprogramming of metabolic gene expression

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Presence and role of Simian Virus 40 (SV40) in malignant pleural mesothelioma

References de Olivera DE. DNA viruses in human cancer: an integrated overview on fundamental mechanisms of viral carcinogenesis. Cancer Lett 2007; 247 : 182-96. Butel JS. Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease. Carcinogenesis 2000; 21 : 405-26. Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008; 319 : 1096-100. Hahn WC, Counter CM

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The Role of Human Insulin Growth Factor (Igf) – Axis in Carcinogenesis

A, Balik E, Kirman I, Remotti H, Ciau N, Jain S, Whelan RL. Insulin-like growth factor binding protein-3 inhibits colitis-induced carcinogenesis. Dis Colon Rectum 2007; 50: 1377-83. [12] Benyoucef S, Surinya KH, Hadaschik D, Siddle K. Characterization of insulin/IGF hybrid receptors: contributions of the insulin receptor L2 and Fn1 domains and the alternatively spliced exon 11 sequence to ligand binding and receptor activation. Biochem J 2007; 40: 603-13. [13] Bouskila M, Hunter RW, Ibrahim AF, Delattre L, Peggie M, van Diepen JA

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Impact of Panax ginseng and Ginkgo biloba extracts on expression level of transcriptional factors and xenobiotic-metabolizing cytochrome P450 enzymes


Introduction: Despite widespread use of Panax ginseng and Ginkgo biloba, the data on the safety as well as herb-drug interactions are very limited. Therefore, we postulate that P. ginseng and G. biloba may modulate the activity and content of cytochrome P450 isozymes involved in the biotransformation of diverse xenobiotic substances. Objective: The aim of our study was to determine the influence of herbal remedies on the expression level of CYP enzymes and transcriptional factors. Methods: Male Wistar rats were given standardized Panax ginseng (30 mg/kg p.o.) or standardized Ginkgo biloba (200 mg/kg p.o.) for 3 and 10 days. The expression in liver tissue was analyzed by realtime PCR method. Results: Our results showed a decrease of CYP3A1 (homologue to human CYP3A4) mRNA level after P. ginseng extract treatment. The CYP2C6 (homologue to human CYP2C9) expression was also reduced. Additionally, after 10 days of the treatment with P. ginseng an increase of CYP1A1 (homologue to human CYP1A1) and CYP1A2 (homologue to human CYP1A2) expression was observed. Moreover, G. biloba extract also caused an increase of expression level for CYP1A1, CYP2C6, CYP3A1 and CYP3A2. Conclusion: Our findings suggest that herbal extracts can modulate the expression of transcriptional factors and CYP enzymes involved in xenobiotic metabolism and chemical carcinogenesis.

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Detection of Mutations in Selected Proto-Oncogenes of Canine Lymphoma


Lymphomas belong among the most frequently diagnosed tumours of the haematopoietic system in dogs. The clinical manifestations and genetic and molecular basis of canine lymphoma resembles those of human non-Hodgkin lymphoma and therefore it can serve as a suitable model for the study of this disease. Neoplastic diseases are the consequence of a number of genetic and epigenetic changes in somatic cells. One of such changes are gene mutations that can subsequently cause changes in the activity of proto-oncogenes and tumour suppressor genes. The aim of our study was to detect potential mutations in selected exons of proto-oncogenes in DNA isolated from samples of lymphoma obtained from two donors - a Bernese Mountain Dog and a female mongrel. On the basis of literary data descriptions of human and canine haematopoietic neoplastic diseases, our investigations of potential changes in DNA focused on proto- oncogenes C-KIT - exons 8, 17; NRAS - exons 1, 2;FLT3 - exons 14, 15 and 20. The investigated samples were amplified by polymerase chain reaction (PCR) and subjected to sequencing. The DNA sequences were compared with reference sequences in the database Ensembl. The comparison of sequences of the C-KIT gene revealed an A/G transition at the 35th nucleotide of exon 8 in the mongrel. It involved a synonymous exchange of the nucleotide in the codon that did not cause a change in the amino acid. In the same sample we recorded several point mutations in the intron regions surrounding the exons 14 and 20 of the FLT3 gene. Changes in the intron regions can affect the expression of genes and thus can play an important role in the origin and development of tumours. No genetic mutations were detected in any gene regions of the Bernese Mountain Dog. In the case of the NRAS gene, no changes were observed in any sample collected from the donors.

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The Full Bibliography of Dietrich Hoffmann

References 1. Hoffmann, D. and E. L. Wynder: Identification of polynuclear aromatic hydrocarbons; 136 th National Meeting of the American Chemical Society (Am. Chem. Soc.), Atlantic City, NJ, 1959, No. 16U. 2. Wynder, E. L. and D. Hoffmann: A Study of Tobacco Carcinogenesis. VII. The role of higher polycyclic hydrocar-bons; Cancer 12 (1959) 1079–1086. 3. Wynder, E. L. and D. Hoffmann: The carcinogenicity of benzofluoranthenes; Cancer 12 (1959) 1194

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Chromatographic Examinations on the Separation of the Alkylating Fractions of Cigarette Tobacco and Smoke/Chromatographische Untersuchungen zur Auftrennung alkylierender Fraktionen des Cigarettentabaks und des Cigarettenrauches

. 6.lmenhorst, H., und Harke, H.-P.: Ober die alkylierende Wirkung des Zigarettenrau~es, in: Zur Methodik der Untersudtuns von Raumkondensaten im Tierversudt; Wissenschaftlid-te Forsdtungsstelle im Verband der Cigarettenindustrie, Hamburg, 1969. 7. Friedman, 0. M., und Boger, E.: Colorimetric estimation of nitrogen mustards in hydrolytic behavior of bis(beta-chloroethyl)amine, nor HN2; Anal. Chem. 33 (1961) 906-<}10. 8. Harington, J. S.: The sulfhydryl group and carcinogenesis, in: Advances in Cancer Researdt, Vol. 10, herausgeg. von

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Research progress of cholangiocarcinoma induced by liver fluke infection

inflammation, thickening of the wall of the tube, and fibrosis around the bile duct. These events eventually develop into epithelial cell carcinoma in the bile duct [ 14 , 15 ]. Keiser et al . [ 16 ] indicated that bile duct carcinogenesis can be induced by injecting a subdose of mutagens into Syria Jintian mouse. It may be the primary antigen of the liver fluke to induce the immune response, leading to the long-term inflammation of the bile duct epithelium to accelerate tumor growth. Zhang et al . [ 17 ] showed that hepatic edema and degeneration, cholangiectasis

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