Bi8110 Genotoxicity and cancerogenesis

Faculty of Science
Spring 2009
Extent and Intensity
2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).
Teacher(s)
prof. RNDr. Jiřina Hofmanová, CSc. (lecturer)
prof. RNDr. Alois Kozubík, CSc. (lecturer)
Guaranteed by
prof. RNDr. Jiřina Hofmanová, CSc.
Department of Experimental Biology – Biology Section – Faculty of Science
Contact Person: prof. RNDr. Jiřina Hofmanová, CSc.
Timetable
Tue 13:00–14:50 BFU
Prerequisites
Passing through lecture of Physiology of cell systems is neccessary
Course Enrolment Limitations
The course is also offered to the students of the fields other than those the course is directly associated with.
fields of study / plans the course is directly associated with
Course objectives
Course gives a complex view of the process of carcinogenesis, including both mutagenic (genotoxic) and epigenetic (non-genotoxic) factors that play a role during the development of cancer (especially colon, breast, prostate cancer and leukemias). It is focused on principles leading to disruptions in signal transduction inside a cell and deregulation of the cell cycle, proliferation, differentiation and apoptosis. Furthermore, it gives an overview of the role of intercellular communications within a tissue (disorders of homeostasis) and the role of environmental factors, such as diet (especially lipid components). Attention is also paid to problems of cancer prevention, diagnosis and therapy.
Main objectives are summarized as follows:
- to understand and explain basic processes resulting in development of neoplastic diseases on the cell and cell population level;
- to understand molecular principles influencing inter- and intracellular communication and transduction of specific signals resulting in cytokinetic changes;
- to understand mechanisms of the effects of environmental factors, especially dietary lipids and lipid metabolism in carcinogenesis;
- to learn principles of use of new research results from described areas for prevention and new therapeutic strategies.
Syllabus
  • Cancer origin and development;
  • Genetic (genotoxic) and epigenetic (non-genotoxic) aspects of carcinogenesis; Carcinogenesis phases - initiation, promotion and progression; genetic and epigenetic factors, carcinogens and cocarcinogens, anticarcinogens; Type of tumours; spontaneous and inducible tumours (oncogenic viruses, chemical and physical carcinogens), benign and malignant tumours, invasion, metastases, tissue clasification.
  • Molecular basis of carcinogenesis;
  • Genetic mechanisms; mutation and mutagens, tumour promoters (exogenous, endogenous); protooncogenes, oncogenes, tumour suppressor genes.
  • Cell transformation; Density-dependent growth inhibition (contact inhibition), differences between normal and transformed cells, changes in the dependence on positive and negative growth factors, malignant transformation.
  • Immortalization; importance of telomers, telomerase and other factors.
  • Non-genotoxic (epigenetic) mechanisms;
  • DNA methylation, histone deacetylation, changes of gene expression; Changes in regulation of proliferation, differentiation and apoptosis; Changes in cell signal transduction; Antiproliferative molecules-association with growth factors, receptors and other members of signal transduction; The role of cell cycle in carcinogenesis; Homeostasis in cell populations; disorders of proliferation, differentiation and apoptosis; apoptosis and necrosis.
  • Cytokine pathological effects;
  • Paracrine and autocrine regulation, disorders in positive and negative regulators, consequences.
  • Importance of oxidative stress; redox balance; activation and deactivation enzymes, pro- and antioxidative systems; oxidative stress; The role of oxidative processes in apoptosis.
  • Cell communication;
  • Extra-, inter- and intracellular communication; the role of gap junctions (GJIC) in tissue homeostasis; disorders in cancer cell communication; decrease of gap junctions; clonal growth; Changes of membrane properties, adhesive properties - cadherins, catenins, integrins, connexins.
  • Metastases;
  • Metastatic cascade, cell-cell and cell-extracellular matrix contacts; changes of adhesive molecules and intracellular signalling; immune system.
  • Angiogenesis; Significance, inducers and inhibitors of angiogenesis.
  • Development of specific cancer types (genetic and epigenetic causes);
  • Hemopoietic disorders - leukemias; Chronic myeloid leukemia, myelodysplastic syndrom, acute leukemia, genetic disorders, disturbing proliferation, differentiation, and apoptosis.
  • The most frequent cancer types - colorectal, breast, prostate and skin cancer;Genetic and non-genetic causes; precancerous stages, etiology, environmental factors;
  • Endogenous carcinogenesis; hormone-dependent cancers.
  • Physiological anticancer mechanisms; The role of immune system, cytostatic and cytotoxic effects of monocytes and macrophages, the effects of cytokines and eicosanoids.
  • Environmental factors in carcinogenesis;
  • Ionizing and non-ionizing radiation; Chemical carcinogens - organic pollutants (aromatic hydrocarbons etc.); Oncogenic viruses and bacterial infection.
  • The effects of harmful environmental factors;
  • Genotoxic vs. non-genotoxic effects (epigenetic toxicity); Disturbed homeostasis - modulation of cytokinetics - causes and consequences, relationship to carcinogenesis; Mechanisms - changes in DNA repair, specific intracellular receptors, oxidative stress, inhibition of GJIC, effects on signal transduction, DNA methylation, changes of expression of oncogenes and tumour suppressor genes.
  • Nutritional aspects of carcinogenesis;
  • Food carcinogens, promotional and antipromotional effects of dietary compounds (vitamins, antioxidants); Content and composition of dietary fat, polyunsaturated fatty acids (PUFAs,n-6 and n-3 types) and their metabolites - eicosanoids etc.; Mechanisms of their effects - mediators and modulators of cell signalling, oxidative metabolism, immune system, interaction of eicosanoids and cytokines; Dietary fiber - short-chain fatty acids - butyrate.
  • Contemporary system of detection of carcinogenic effects of compounds;
  • Genotoxicity (mutagenic effects) – mutagenicity tests; Problems of detection of non-genotoxic carcinogens; long-term test with laboratory animals, alternative short-term tests - transformation test, changes of proliferation and apoptosis in tissues, GJIC changes, detection of specific biomarkers (specific cell enzyme and receptors activities);
  • Models of carcinogenesis - studies of initiation and promotion effects - skin, liver, bladder, kidney; causes of different sensitivity of cells, tissues and organisms to carcinogens; Risk assesment - dose-response curves, threshold values, the effects of mixture of compounds (additivity, synergism, antagonism).
  • Importance of experimental ecotoxicology - perspectives, association with experimental and predictive oncology.
  • Cancer prevention, diagnostics and treatment;
  • Experimental, epidemiological and clinical studies, population screening; genetic predisposition, life-style; Therapy - surgery, radiation, chemotherapy, immunotherapy.
  • Predictive oncology;
  • Tumour standardization, diagnostic markers, prognostic vs. predictive factors; Detection of specific parameters - cytokinetic parameters, molecular markers; Modern methods (flow cytometry,laser scanning, molecular methods, microarrays), detection of proliferation activity and apoptosis; Comparison of the methods and interpretation of measured parameters; Data management - importance of specific statistical analyses.
Literature
  • ALBERTS, Bruce. Základy buněčné biologie : úvod do molekulární biologie buňky. Translated by Arnošt Kotyk. 2. vyd. Ústí nad Labem: Espero Publishing, 2004, xxvi, 630. ISBN 8090290620. info
  • ALBERTS, Bruce. Molecular biology of the cell. 3rd ed. New York: Garland Publishing, Inc., 1994, xliii, 129. ISBN 0-8153-1620-8. info
  • FÖLSCH, U. R., K. KOCHSIEK and R. F. SCHMIDT. Patologická fyziologie. Vyd. 1. Praha: Grada Publishing, 2003, 586 s. ISBN 80-247-0319-X. info
  • Nutritional oncology. Edited by David Heber. 2nd ed. Amsterdam: Elsevier-Academic Press, 2006, xxiv, 822. ISBN 0120883937. info
  • Functional metabolism, Regulation and adaptation, Ed. K. B. Storey, Wiley-Liss, Inc., Hoboken, New Jerswy, 2004
  • Signaling networks and cell cycle control : the molecular basis of cancer and other diseases. Edited by J. Silvio Gutkind. 1st ed. Totowa: Humana Press, 2000, xiv, 578. ISBN 089603710X. info
  • Cell cycle and growth control : biomolecular regulation and cancer. Edited by Gary S. Stein - Arthur B. Pardee. 2nd ed. Hoboken, N.J.: Wiley-Liss, 2004, xiii, 800. ISBN 0471250716. info
  • Apoptosis and Cancer Therapy, Vol. 1 and 2, Eds. K.M. Debatin, S. Fulda, WILEY-VCH Verlag GmbH&Co.KgaA, Weinheim, 2006
  • ADAM, Zdeněk, Jiří VORLÍČEK and Jana KOPTÍKOVÁ. Obecná onkologie a podpůrná léčba. Praha Publishing: Grada, 2003, 788 pp. ISBN 80-247-0677-6. info
  • KLENER, Pavel. Klinická onkologie. 1. vyd. Praha: Galén, 2002, xxxvii, 68. ISBN 802460468X. info
  • KREJSEK, Jan and Otakar KOPECKÝ. Klinická imunologie. 1. vyd. Hradec Králové: NUCLEUS HK, 2004, 941 s. : i. ISBN 80-86225-50-X. info
  • HALLIWELL, Barry and John M. C. GUTTERIDGE. Free radicals in biology and medicine. 4th ed. Oxford: Oxford University Press, 2007, xxxvi, 851. ISBN 9780198568681. info
  • + doporučené speciální separáty a schemata z přednášek
Assessment methods
lectures final written exam
Language of instruction
Czech
Follow-Up Courses
Further Comments
Study Materials
The course is taught annually.
The course is also listed under the following terms Spring 2008 - for the purpose of the accreditation, Spring 2011 - only for the accreditation, Spring 2003, Spring 2004, Spring 2005, Spring 2006, Spring 2007, Spring 2008, Spring 2010, Spring 2011, Spring 2012, spring 2012 - acreditation, Spring 2013, Spring 2014, Spring 2015, Spring 2016, Spring 2017, spring 2018, Spring 2019, Spring 2020, Spring 2021, Spring 2022, Spring 2023, Spring 2024, Spring 2025.
  • Enrolment Statistics (Spring 2009, recent)
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