毒理学基础个人总结 Chapter 9 Chemical carcinogenesis.docxVIP

Chapter 9 Chemical carcinogenesis Part 1 Introduction Historical Background Chemical carcinogenesis has been noted for over 200 years. 1761, Hill found relation between tobacco snuff and nasal cancer 1775, Port identified scrotum cancer cases in soot-exposing chimney sweeps. 1895, Rehn discovered that bladder tumors occurred in aniline dye-exposing workers (β-naphthylamine being the involved carcinogen). In modern times, dozen of chemicals and physical factors have been identified as human carcinogens. Facing the ever increasing risk of tumor upon human beings, governments, industries and academic institutions all over the world are now striving for prevention and treatment of various life-threatening tumors. Fundamental Concepts Carcinogenesis Is the process of cancer development Chemical carcinogenesis deals with both the mechanisms for carcinogens to induce cancer and the experimental systems to detect unknown carcinogens. Cancer here does not mean merely carcinoma originated from epithelial tissues, but represent neoplasm of all types. Carcinogen It has been estimated that about 90% of human cancers are caused by environmental factors, predominantly chemical carcinogens. Part 2 Mechanism of Chemical Carcinogenesis Metabolism of Chemical Carcinogens in Relation to Carcinogenesis Most carcinogenic chemicals per se (by themselves) are inactive, they need metabolic activation before exerting biological effects. Important terms related to bioactivation： Procarcinogen Proximate carcinogen Ultimate carcinogen Direct acting carcinogen Interaction with Macromolecules Covalent binding of the reactive metabolites of chemicals to macromolecules, such as DNA, which may lead to point mutations, frameshift mutations and other damages. These changes may or may not be persistent ― they can be reversed by error-free DNA repair or disappear by apoptosis of the involving cells, otherwise mutations can be retained and expanded through cell division. Oncogene Hypothesis(学说