Carcinogenesis (Jahn).pdf

Carcinogenesis Stephan C. Jahn, Ph.D. Carcinogenesis Chemical Carcinogenesis Many chemicals are capable of causing cancer May work through genotoxic or non-genotoxic mechanisms Come from many different sources  Industrial/lab exposure  Lifestyle Smoking...

Carcinogenesis Stephan C. Jahn, Ph.D. Carcinogenesis Chemical Carcinogenesis Many chemicals are capable of causing cancer May work through genotoxic or non-genotoxic mechanisms Come from many different sources  Industrial/lab exposure  Lifestyle Smoking Eating  Environment Everyday things Carcinogen Testing In vivo  Testing for tumor formation in mice and rats In vitro  Ames test Most commonly used Tests ability to cause DNA mutations Uses a special strain of bacteria  Human cell line testing Ames Test Histidine [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)] Role of Chemical Carcinogens in Human Cancer The Biology of Cancer By Emanuel Mazor, Robert A Weinber Smoking and Carcinogenesis PAH: Polycyclic aromatic hydrocarbons formed in tobacco processing and by combustion NNK: Nicotine mutagen formed in tobacco processing Carcinogens in Tobacco Carcinogen/DNA Interaction Would You Like Fries with Your Cancer? Food cooked at high temperatures (grilling/frying) causes the formation of carcinogens  Smoke from grill contains benzopyrene Cigarette = 17 ng Grilled Steak = 2200 μg (~130,000x)  Proteins themselves become mutagenic Viral Carcinogenesis ~18% of cancers are caused by viruses  Epstein-Barr, Hepatitis-B, Hepatitis-C, HPV, Kaposi sarcoma associated herpes virus, HIV Cancer can be caused on purpose  Some viruses need replicating cells to reproduce  HPV Cancer can be caused on accident  Viralgene gets randomly inserted into human gene  HIV, other retroviruses HPV Infection and Cancer Virus codes for 8 proteins 6 early  2 late Late proteins named E6 and E7  Bind to and inhibit p53 and Rb HIV Infection and Cancer Any retrovirus can cause cancer Viral genes are inserted in human chromosomes Can disrupt genes  Can mutate tumor suppressor  Can activate oncogene Tumor Suppressor Tumor HIV Suppressor Proto-oncogene Viral Protein Oncogene Viral Promoter Radiation Induced Carcinogenesis Radiation causes DNA damage Single/Double strand breaks Thymine dimers Majority of damage is fixed Small errors build up over time