Society of Toxicology



Eminent Toxicologist lectureSamuel M. Cohen, MD, PhD – Chemical CarcinogenesisNotes prepared by Wade H. PowellLearning Objectives:Students should be able to:Understand how cancer risk is heritableExplain the function of oncogenes and Tumor Suppressor GenesUnderstand and analyze alternative models for the development of cancer.Explain the relationship between DNA damage and Cell division in the emergence of cancer. How to DNA reactive and Non-DNA reactive carcinogens differ?Apply the concept of dose responsiveness to chemical carcinogenesis: Why is it unnecessary to completely eliminate exposure to chemical carcinogens?Understand different carcinogenicity tests and their assumptions.Evaluate the relevance to of a carcinogenicity test to human risk assessment.Recommended prerequisite topicsIntroductory biology-genetics, enzyme functionBasic molecular cell biology: DNA replication and repair; stem cells and differentiationBasic enzyme function.Study questionsName and explain at least two specific examples of hereditary influences on the development of cancer.Dr. Cohen states that “Cancer Arises Due to “Bad Luck.” What factors influencing carcinogenesis are beyond the control of an individual? What factors in carcinogenesis are not merely random?What is meant by “metabolic activation” of a chemical carcinogen?Rodents are often used for testing the carcinogenicity of a chemical. Explain the advantages and disadvantages of rodent models for predicting effects in humans. What basic assumptions underlie the use of bioassays for human risk assessment of potential chemical carcinogens? Are these assumptions valid? How is human relevance of animal testing established?Application of this Lecture to Vision and Change Core Concepts and Competencies. Core ConceptsEvolutionStructure and FunctionInformation flow, exchange, and storageThe role of heritability and mutations in the development of cancer.Pathways and transformations of energy and matterMetabolic activation of chemical carcinogensSystemsThe relationship between exposure level, DNA damage, stem cell division, differentiated cell division, and cancer. Core CompetenciesAbility to apply the process of science.Evaluating the quantity and quality of evidence surrounding the carcinogenicity of a chemical.Ability to use quantitative reasoningUnderstanding the relationship between exposure level, exposure incidence, and exposure timing in the development of cancer.Ability to use modeling and simulationConstruction of multi-stage models of carcinogenesis. Ability to tap into the interdisciplinary nature of scienceCarcinogenesis integrates concepts of molecular biology, cell biology, enzymology, physiology, and development.Ability to communicate and collaborate with other disciplinesAbility to understand the relationship of science and societyPublic understanding of exposure level and chemical carcinogenicity.Vision and Change Core Concepts.Evolution. The diversity of life evolved over time by processes of mutation, selection, and genetic change. Structure and Function. Basic units of structure define the function of all living things. Information flow, exchange, and storage. The growth and behavior of organisms are activated through the expression of genetic information in context.Pathways and transformations of energy and matter. Biological systems grow and change by processes based upon chemical transformation pathways and are governed by the laws of thermodynamics.Systems. Living systems are interconnected and interacting. Core Competencies and Disciplinary Practice. Ability to apply the process of science. Biology is evidence based and grounded in the formal practices of observation, experimentation, and hypothesis testing.Ability to use quantitative reasoning. Biology relies on applications of quantitative analysis and mathematical reasoning.Ability to use modeling and simulation. Biology focuses on the study of complex systems.Ability to tap into the interdisciplinary nature of science. Biology is an interdisciplinary science.Ability to communicate and collaborate with other disciplines. Biology is a collaborative scientific discipline.Ability to understand the relationship of science and society. Biology is conducted in a societal context. ................
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