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12151 - Carcinogenesis Tee L Guidotti Dept of Environmental...

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Carcinogenesis Tee L. Guidotti Dept. of Environmental and Occupational Health GWUMC
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Characteristics of Toxicological Mechanisms Carcinog. Immune Toxicity Target Genome Immune Receptor Thres- hold ? No Threshold Recog- nition Threshold, dose-dep. Outcome Stereotyp Stereotyp Multiple Response Stochastic Nonstoch. Dose-dep. Latency Long Short Variable
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Characteristics of a Cancer Uncontrolled growth beyond normal hyperplasia in vivo loss of cell-cell inhibition in vitro anaplasia (highly variable) apoptosis (normal cell death) defective Tendency to invade surrounding tissue Tendency to travel beyond site of origin metastasis may occur late
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Early Theories of Carcinogenesis Surfeit of black bile (Hippocrates) Omnis cellula ex cellula (Bichat, Pasteur) Irritation hypothesis (Virchow) medicolegal issues persists as lay theory Embryonic hypothesis (teratomas, etc.) Parasitic hypothesis
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Recent Theories of Carcinogenesis Chemical carcinogenesis derived from observations by Pott, 1775 major line of mechanistic oncology every since Viral theory of carcinogenesis Two-stage mechanism of Ca.genesis two processes: initiation, promotion followed by progression
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Steps in Chemical Carcinogenesis 1. Biotransformation 2. Initiation: Covalent binding to DNA 3. Fixation: Mutation stabilized by mitosis 4.
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