E0240 Biomarkers and Toxicity Mechanisms

Přírodovědecká fakulta
jaro 2020
Rozsah
2/0/0. 2 kr. (plus ukončení). Ukončení: zk.
Vyučující
prof. RNDr. Luděk Bláha, Ph.D. (přednášející)
doc. RNDr. Pavel Babica, Ph.D. (přednášející)
Garance
prof. RNDr. Luděk Bláha, Ph.D.
RECETOX - Přírodovědecká fakulta
Kontaktní osoba: prof. RNDr. Luděk Bláha, Ph.D.
Dodavatelské pracoviště: RECETOX - Přírodovědecká fakulta
Omezení zápisu do předmětu
Předmět je nabízen i studentům mimo mateřské obory.
Mateřské obory/plány
Cíle předmětu
The objectives of the course are to provide an overview of major mechanisms of toxicity of chemical compounds and outline the principles and methods in the exploration of biomarkers of effects.
Výstupy z učení
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 interprete 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
Osnova
  • The course advances the knowledge in toxicity mechanisms (MoA – modes of action) of major toxic classes of compounds (examples are provided at individual MoAs). Methodological aspects are addressed in detail in other complementary classes focused on in vitro toxicity. It is an advanced course lectured in English, and recommended primarily for MSc. or PhD students.
  • Schedule (12 weeks of regular semester):
  • 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). Overview of approaches of in vivo and in vitro studies.
  • 3. Proteins as targets of toxic compounds. Enzymes and their inhibitions (examples of toxic MoAs), non-specific and specific (key-lock) effects.
  • 4. Phospholipids and membranes as targets of toxicants. Polar and non-polar narcosis, membrane gradients and their disruption, membrane receptors and related toxic effects.
  • 5. Metabolism of xenobiotics. Drug-metabolising enzymes, activation and detoxication. Cytochromes P450 - classes, polymorphism, induction and toxicological importance. Enzymes of phase II of biotransformations. Antioxidant compounds and processes.
  • 6. 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.
  • 7. Cytotoxicity – necrosis and apoptosis. Common mechanisms of toxicity in cells, adverse effects in energy metabolism, toxicity to biomembranes, specific mechanisms of cytotoxicity. Importance of apoptosis, controling, possibilities of model modulations of basic processes.
  • 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. Endocrine disruption and related mechanisms. Dioxin like toxicity (AhR), estrogenicity (ER), and other nuclear receptor-dependent mechanisms and toxic outcomes.
  • 10. Biomarkers of exposure and susceptibility to toxic compounds. Evolutionary and physiological adaptations. Adducts of toxicants with biomolecules and their assessment. Detoxification processes as biomarkers, examples of CYPs and their role.
  • 11. Biomarkers of toxic effects I – In vivo biomarkers - Behavioral and Clinical biomarkers, Imunohistopathology, Clinical chemistry and hematology, Enzyme changes, Gene and protein expression biomarkers, Oxidative stress markers
  • 12. Biomarkers of toxic effects II – Omics and toxicogenomics effect biomarkers. Approaches in development and validation of biomarkers. Case studies and examples.
Literatura
  • MacGregor J.T. et al.: Strategies and testing methods for identifying mutagenic risks. Mutation Research 455, 3-20, 2000.
  • PREEDY, V.R. a 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 a Ivan HOLOUBEK. Environmental xenobiotics and nuclear receptors-Interactions, effects and in vitro assessment. Toxicology in vitro, 2005, roč. 20, č. 1, s. 18-37. ISSN 0887-2333. info
Výukové metody
Lectures (weekly), supported by exmamples and discussion of case studies. E-learning materials provided in the IS.MUNI.CZ system.
Metody hodnocení
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%.
Vyučovací jazyk
Angličtina
Další komentáře
Studijní materiály
Předmět je vyučován každoročně.
Výuka probíhá každý týden.
Předmět je zařazen také v obdobích podzim 2020.