Bi6882 Biomarkers and toxicity mechanisms

Faculty of Science
Autumn 2016
Extent and Intensity
2/0/0. 2 credit(s) (plus extra credits for completion). Type of Completion: zk (examination).
Teacher(s)
prof. RNDr. Luděk Bláha, Ph.D. (lecturer)
Sergio Jarque Ortiz, Ph.D. (seminar tutor), prof. RNDr. Luděk Bláha, Ph.D. (deputy)
Guaranteed by
prof. RNDr. Luděk Bláha, Ph.D.
RECETOX – Faculty of Science
Contact Person: prof. RNDr. Luděk Bláha, Ph.D.
Supplier department: RECETOX – Faculty of Science
Timetable
Mon 19. 9. to Sun 18. 12. Wed 14:00–15:50 D29/252-RCX1
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
At the end of the course students will be able to:
- understand major mechanisms of effects of foreign compounds in the organisms and the applications as the biomarkers.
- define the most important biochemical and cellular processes involved in genotoxic as well as non-genotoxic effects.
- recognize and classify major classes of xenobiotics with the focus on major classes of environmental contaminants, newly emerging cytostatic and chemoprotective drugs.
- discuss and interpret biochemical markers of susceptibility, exposure and effects.
- use experimental methods of in vivo and in vitro biomarkers.
- know examples of practical applications of biomarkers in toxicology, ecotoxicology, and molecular epidemiology
Syllabus
  • 1. Mechanisms of toxicity and biomarkers - introduction to effects of xenobiotics in organisms, toxokinetics and toxodynamics. Effects at different organismal levels - importance of biochemical processes. Biomarkers of exposure, effects and susceptibility. 2. Major classification of adverse effects (genotoxicity vs. non-genotoxic mechanisms, organ specific toxicity). Approaches and principles of the studies in vivo and in vitro. 3. Metabolism of xenobiotics. Drug-metabolising enzymes, activation and detoxification. Cytochromes P450 - classes, polymorphism, induction and toxicological importance. Enzymes of phase II of biotransformations. Antioxidant compounds and processes. Biomarkers of exposure and susceptibility. 4. Genotoxic effects. DNA and its importance, mutations and other adverse chemically induced genotoxic effects. Strategies, possibilities and methods of genotoxicity testing. Genotoxicity of xenobiotics in risk assessment. Biomarkers of exposure and effects. 5. General cytotoxicity - necrosis. Common mechanisms of toxicity in cells, adverse effects in energy metabolism, toxicity to biomembranes, specific mechanisms of cytotoxicity. Methods and studies of cytotoxicity in vitro. 7. Programmed cell death - apoptosis. Importance of apoptosis, controlling, possibilities of model modulations of basic processes. Inhibition of apoptosis - an important mechanism of toxicity of xenobiotics. 8. Cell proliferation, modulations of signal transductions, cell cycle. Major processes of non-genotoxic carcinogenesis, transformation and clonal expansion, inhibition of intercellular communication (GJIC). Chemically induced carcinogenesis. 9. Methods for detection and studies of non-genotoxic mechanisms. Dioxin like toxicity, estrogenicity, other mechanisms of endocrine disruption, activation of signalling pathways, oxidative stress, modulation of cell proliferation. Use as biomarkers of exposure and effects. 10. Neurotoxicity and immunotoxicity. Examples and importance of toxic effects, relations of organ-specific toxicity to common biochemical mechanisms of toxic effects. Case studies and methods, specific biomarkers in vivo. 11. Toxicity mechanisms of major xenobiotics: PAHs, PCBs, PCDD/Fs, organochlorine contaminants, detergents, inorganic pollutants, cytostatic and chemoprotective drugs.
Literature
  • MacGregor J.T. et al.: Strategies and testing methods for identifying mutagenic risks. Mutation Research 455, 3-20, 2000.
  • PREEDY, V.R. and V.B. PATEL. General Methods in Biomarker Research and their Applications (Biomarkers in Disease: Methods, Discoveries and Applications). Springer, 2015. info
  • KEWAL, K.J. The Handbook of Biomarkers. Humana Press, 2015. info
  • Nuclear receptors. Edited by Margaret K. Bates - Regina M. Kerr. Hauppauge, N.Y.: Nova Science, 2011, xiii, 185. ISBN 9781620819715. info
  • JANOŠEK, Jaroslav, Klára HILSCHEROVÁ, Luděk BLÁHA and Ivan HOLOUBEK. Environmental xenobiotics and nuclear receptors-Interactions, effects and in vitro assessment. Toxicology in vitro. 2005, vol. 20, No 1, p. 18-37. ISSN 0887-2333. info
Teaching methods
Lectures (weekly), supported by e-learning materials in the IS.MUNI.CZ system
Assessment methods
The evaluation is based on (i) final written test - 10 open questions (50% success required as minimum), followed by (ii) oral examination (2 broader questions, which test the ability of students to independently think and express themselves). The weights of the written test and oral examination are 70:30%.
Language of instruction
English
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 2009, Spring 2010, Spring 2011, Spring 2012, spring 2012 - acreditation, Spring 2013, Spring 2014, Autumn 2014, Autumn 2015, autumn 2017, Autumn 2018.
  • Enrolment Statistics (Autumn 2016, recent)
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