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Percival Pott 1775, described cancer of the scrotum in chimney sweeps. They used to call it soot wart Clunet 1910, in france demonstrated that when rats are exposed to x-rays they get cancer 1914 was found that it causes cancer in humans Yamagiwa and Ichikawa 1915, cancer of the skin by prolonged application of coal tar to rabbit's ears Kennaway 1930, isolated highly carcinogenic polycyclic hydrocarbons crom coal tar Rehm 1895 described bladder cancer in aniline dye workers Hueper 1938, showed that 2-naphthylamine caused cancer of the bladder when administered to dogs. how did turkeys, ducks and chickens get liver cancer? 1961, england. they were fed peanuts that were contaminated by aspergillus flavus, a fungus. The fungus produced aflatoxin, a potent cancer-inducing agent in the liver Why is liver cancer so prevalent in africa and asia, while colon cancer is really prevalent in North America? liver cancer is from a high incidence of hepatitis B and contamination of foods by aflatoxin colon cancer is apparently associated with a western diet, high in saturated fat and low in fibre, fresh fruit and vegetables Tobacco smoke and cancer 30% of all cancer deaths in the lung, upper respiratory tract, esophagus, bladder and pancreas -depends on the tar content of the cigarettes, frequency of smoking and duration of habit how many times more likely are smokers to get lung cancer compared to non smokers? 8 times what is the latent period between smoking and lung cancer? 20 years Diet and cancer colon, rectum and prostate cancer: saturated animal fat and red meat stomach cancer: salt you are more likely to get cancer if: you are fat and don't exercise enough you skimp on fresh vegetables and fruits Infections and cancer dna viruses are responsible for inducing some cancers hepititis A and C: liver cnacer HPV: cancer of the cervix epstein-barr virus: lots HIV: Kaposi's sarcoma how much of the global liver cancer has been caused by hepititis? 80% what has been associated with stomach cancer and stomach ulcers? the bacteria helicobacter pylori arsenic cancers lung and skin asbestos cancers lung benzene cancers leukemia diesel exhaust cancers lung formaldehyde cancer nose man made mineral fibres lung hair dyes bladder ionizing radiation bone marrow cancer mineral oils skin non arsenical pesticides lung painting materials lung polychlorinated biphenyls (heat transfer and hydraulic fluids and lubricants) liver, skin radon lung soot skin How does cancer happen a carcinogen, unactivated, gets into our bodies and undergoes metabolic activation. Now it is an "ultimate carcinogen" the ultimate carcinogen reacts irriversible with our dna causing a change in the chemistry of the gene. A mutation has been induced what are the three different categories of carcinogens? 1. initiators 2. promoters 3. progressors what kind of carcinogen are chemicals? initiators-they damage genes involved in control of cell division and facilitate the division and proliferation of cells How does cancer arise? when a single cell accumulates a number of mutations and escapes restraints on cell division what do promoter carcinogens do? they don't damage genes but selectively enhance the growth of cancer cells or precursors of cancer cells what do progressor carcinogens do? allow the rapid growth of tumors once they are established What is the delaney amendment? 1958, and amendment to the food and drug act in the US. Prohibits the use of foodstuffs of any substance that has been shown at any dose to produce cancer in any experimental animals what is the only officially recognized way to test a chemical for carcinogenicity? determine whether it causes cancer in experimental animals. Lots of time and monaaaay required. What is the Ames test? a cheaper cancer test developed by Bruce Ames at the University of Berkely, California. takes a mutant of the bacteria salmonella typhimurium that has lost the ability to make the amino acid histidine. When it is exposed to a mutagenic chemical, the original defect is repaired and it continues making histamine. so you know if it starts making histamine again, that the chemical you added was a carcinogen What are the six categories of cancer treatment? surgery chemotherapy radiation biological therapies hormone blocking/supplementing bone marrow transplantation What are the few cancers that they have been able to cure? testicular cancer, hodgkin's disease (cancer of the lymph) and childhood leukemias) what are the 5 goals of cancer chemotherapy 1. cure 2. prolonging survival 3. relief of symptoms 4. psychological support 5. clinical research to improve things in the future How do the drugs used in cancer chemotherapy work? they kill tumour cells by inhibiting protein synthesis or cell division (mitosis) What are the adverse effects of cancer chemotherapy? the drugs also harm rapidly dividing normal cells in the body. ex: bone marrow cells which are the source of red and white blood cells as well as platelets in the blood. Develop cytopenia also: cells lining the gastrointestinal tract..so you get nausea and vomiting and ulceration finally: hair cells. bald How do they determine the dosage and schedule of cancer chemotherapy? designed to maximize the anticancer effect while minimizing toxicity Why do they often use a combination of chemotherapy drugs at once? cancer cells are less likely to defend themselves when attacked by a variety of drugs that attack in different ways also each drug has different toxicities. So you can give a smaller dose of a bunch of drug and keep the toxicities less severe then giving a lot of one drug and having huuuuge consequences What are the seven classifications of cancer chemotherapy drugs? 1. alkylating agents 2. antimetabolites 3. natural products 4. antibiotics 5. hormones 6. biologicals 7. miscellaneous alkylating agents used in chemotherapy alkylate dna thereby damaging it. ex: nitrogen mustard, mechlorethamine antimetabolites used in chemotherapy disrupts cellular metabolism ex: methotrexate which is a folic acid antagonist natural products in chemotherapy vincristine isolated from the periwinkle plant. arrests cell division paclitaxel isolated from the western yew, also arrests cell division (ovarian and breast cancer) antibiotics in chemotherapy doxorubicin-acts by damaging dna hormones in chemotherapy prednisone-suppresses cell division tamoxifen suppresses the effect of estrogen (helps to prevent breast cancer) biologicals in chemotherapy block cytokines..that control cell growth. Some of them are also antibodies to the cytokines procarbazine in chemotherapy damages DNA