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Lecturer(s)
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Vondráček Jan, prof. RNDr. Ph.D.
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Course content
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Molecular toxicology focuses mainly on the study of molecular and cellular responses that mediate toxicity of analyzed compounds. Its findings contribute not only to elucidation of basic mechanisms of toxicity, but also provide a mechanistic basis for our understanding of systemic toxicity, which is essential for a proper risk estimation and hazard control. Modern molecular toxicology studies also help to identify many physiological mechanisms of regulation of cellular functions underlying the complex chemical?biological interactions within living systems. The program of the course aims to provide students with a basic understanding of mechanisms contributing to the toxic action of xenobiotics negatively affecting cellular functions, as well as to prvide them with an overview of state-of-the-art methodology used for analysis of mechanism of toxic action at both cellular and molecular levels.
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Learning activities and teaching methods
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Lecture
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Learning outcomes
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Principle goal of this course is to enable the students to understand the principles of modulations of cellular processes in organism by toxic compounds. They should be able to make deductions based on the acquired knowledge in molecular toxicology, in order to interpret molecular mechanisms underlying the effects of toxic compounds within organism. At the end of this course, students should also have a basic understanding of metabolism of xenobiotics within organism, their intearactions with intracellular receptors, direct or indirect inetractions with cellular components, and basic types of toxic responses.
The course program extends the course Basic Toxicology (KBB/ZTOX) and upon the completion of the Molecular Toxicology course, the students is able to: - describe the toxicity mechanisms based on the impact of toxicants on intracellular receptors and control of gene expression; - describe and define the mechanisms of regulation of the major receptor systems mediating effects of toxicants (cell surface receptors, Ah receptor, PAS proteins, pregnane X receptor, constitutive androstane receptor, peroxisome proliferator-activated receptors, interactions among the receptors activated by xenobiotics); - describe and define mechasnisms of toxicity linked with direct interactions with cellular macromolecules and cellular stress; - describe and define the factors contributing to susceptibility towards toxic environmental factors affecting organisms; - describe and define the impact of toxicants on intracellular signaling (activity of protein kinases, redox signaling, hypoxia, deregulation of cell cycle and programmed cell death, effects on signal transducers etc.); - describe and explain basic principles of modern methods of analysis of toxicity mechanisms and predictive assays (principles of toxicogenomics, proteomics and metabolomics in the area of investigation of toxicity mechanisms at cellular and molecular levels).
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Prerequisites
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For a successful completion of the course, it is necessary to posses basic working knowledge of biochemistry, cell biology and toxicology.
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Assessment methods and criteria
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Written exam, Didactic Test
50% test in extent of lectures
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Recommended literature
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Josephy P.D. a Mannervik B. (2006). Molecular toxicology.
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Ramos K. (2010). Cellular and Molecular Toxicology (Comprehensive Toxicology vol. 2). Elsevier.
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Smart R.C. a Hodgson E. (2018). Molecular and Biochemical Toxicology. Hoboken, NJ, USA.
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