Most environmental causes of cancer are mutagens: mutagenic compounds, X-rays, uv Enzymatic conversion ve epoxide Spontaneous reaction with N7 of guanosine i H 3 C O O O O O O to react H 3 C O O Aflatoxin B O O O HO O O N + HN G H 2 N N 3,4-benzpyrene N DNA Cancer tends to arise in actively dividing cells ? Epithelial cells (lining of intestine, lungs etc.) = carcinoma ? Blood and lymphatic cells = lukemia, meyloma, lymphoma ? Connective tissue (bones, tendons muscle) = sarcoma Cancer is a genetic disease of somatic cells The underlying cause is mutations that release cells from the normal constraints that exist in well organized tissues allowing uncontrolled growth Which are the key genes that are mutated ? Incidence of stomach cancer as a function of age 0 100 200 300 400 500 600 700 800 0 5 10 3020 2515 35 5545 5040 60 80 85 70 7565 Age (1992) Stomach Cancer Rate per 100,000 Females Females (1975) Males (1992) Males (1975) Incidence of stomach cancer as a function of age. Figure by MIT OCW. Major complications in understanding the genetic basis of cancer ? Multiple mutations are necessary to produce a tumor cell ? Different types of tumor have different genes mutated ? Early initiating events occur rarely in complex tissues and are therefore extremely difficult to detect ? The key initiating event often leads to an increase in mutation rate thus tumor cells often bear many fortuitous mutations Important aspects of the disease we won't discuss relate to the spread of cancer cells and the formation of large tumors (metastasis and angiogenesis) 3T3 cells in culture Transformed 3T3 cells Images removed due to copyright reasons. Isolation of the Ras oncogene from human tumor cells Figure by MIT OCW. Synergistic effect of oncogenic forms of myc and ras 100 80 60 40 20 0 i D D Tumor-free m ce (%) myc ras myc + ras 0 50 100 150 200 Age (days)