Mechanisms of cancer induction by environmental carcinogens and chemoprevention by natural and synthetic agents. BCHEM 510 BCHEM 510 Carcinogenesis and Chemoprevention (2) The etiology of most human cancer remains obscure even though a vast body of literature describes risk factors for certain cancers and proposes various hypotheses for cancer etiologyon the basis of epidemiological and experimental studies . Tobacco smoking is an established cause of several cancers, with lung cancer remaining the first target on the list. International studies have repeatedly confirmed that people (Chinese, Japanese) migrate from their country of origin to the U.S., adopt the pattern of certain cancers within a few generations (e.g., breast and prostate) of the latter country, which is indicative of the presence of chemical carcinogens in the environment and/or changes in lifestyles. Consequently, the search for carcinogens that exist in the human environment challenges both scientists and regulatory agencies. Chronic exposure to traces of chemical carcinogens in the diet, in polluted air, or in tobacco smoke can be important in the etiology of several human cancers in the presence of host factors that favor the multi-step process of carcinogenesis. Bioassays in laboratory animals can provide important information on the role of environmental agents in the induction of particular types of cancer. Biochemical studies can lead to insights into the nature of interactions of these environmental agents with macromolecules such as DNA that are necessary, but not always sufficient for carcinogenesis.The search for optimal diets and for naturally occurring agents in routinely consumed foods that may inhibit cancer development, although challenging, constitutes a valuable and plausible approach to finding ways to control and prevent cancer. The prevention of cancer is the longstanding goal for most cancer researchers. There has been enormous gain in our understanding of carcinogenesis and cancer progression; such knowledge has provided new and promising opportunities to prevent cancer, e.g., to treat pre-cancer or inhibit carcinogenesis (a process often involving 20-30 years in human epithelial cancers), rather than waiting to treat cancer. In the early 1980's, the U.S. National Cancer Institute recognized the promise of chemoprevention research. In summary, this course will provide a better understanding of the potential contribution of environmental carcinogens in the development of certain human cancers and will provide important information on cancer chemoprevention intervention strategies.The co ruse will cover topics that include exposure, metabolic activation, detoxification, and biomonitoring of chemical carcinogens in the human environment, carcinogen-induced DNA damage, mutagenesis and DNA repair, carcinogen-induced cellular and molecular alternations, tumorigenesis and organ specificity in laboratory animals, and factors modulating individual susceptibility to the deleterious effects on chemical carcinogens. Furthermore, this course will provide knowledge on various classes of cancer chemopreventive agents, their efficacy, safety, and mechanisms of action in preclinical studies.Course Objectives: Upon completion of this course, the students will be able to: 1. Understand the potential risk associated with human exposure to chemical carcinogens detected in the environment. 2. Describe the current assays of biomonitoring of human exposure to chemical carcinogens. 3. Learn the process of metabolic activation and detoxification of chemical carcinogens. 4. Understand the stages of the multi-step carcinogenesis process. 5. Identify factors that govern individual susceptibility to the deleterious effects of chemical carcinogens. 6. Understand the concept of cancer chemoprevention. 7. Identify molecular and cellular targets for chemoprevention intervention at any time during the process of carcinogenesis.Grading: Grading will be determined as follows: 1. Midterm Exam 30% 2. Research Paper* 30% 3. Class Participation 10% 4. Final Exam 30% Total 100%*Guidelines for Research Paper: The topic will be selected following approval of the faculty member in charge. The paper should include the goals (aims) of the research project, literature background, the significance of the research topic, knowledge to be gained, gaps in existing knowledge, and the potential to propose future studies. Faculty Member Proposing:Karam El-Bayoumy
