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CANCER Cells can lose control of cell division & growth or cell death If they grow unchecked, they form tumours TUMOURS Tumours are groups of cells – can be benign or malignant Benign tumours divide for a period then stop. They can be removed by surgical or laser methods Malignant tumours never stop dividing, they cause angiogenesis (blood vessels grow into them). This provides them food and oxygen to allow them to keep growing. It also allows the cancer to spread. CANCER Cancers begin as a primary tumour. However, cells break away from the primary tumour and - travelling in blood and lymph - establish metastases in other locations of the body. Many tumours is more difficult to target treatment then a single tumour. Cancer Statistics Scottish Statistics Cancers follow from faulty (mutated) genes Faulty genes can be inherited Exposure to agents which damage DNA increase the chances of a mutation occurring e.g » Chemicals e.g. cigarette smoke » Radiation e.g UV, Xray, Gamma rays In addition, damage to repair and checking systems will increase the chances of cancer CAUSES OF CANCER The development of cancer is associated with a variety of risk factors Tobacco Sunlight (UV irradiation) Body weight Physical activity Diet Hormones Occupations Infections Tobacco Sunlight Exposure Diet Body Weight Physical Activity Hormones Occupation Infection http://news.bbc.co.uk/1/hi/health/8102621.s tm “In fact, scientists estimate about a third of the most common cancers could be prevented if people ate healthily, maintained a healthy weight and were regularly physically active “ 2 sets of genes control cell division: Proliferation genes (proto- oncogenes) speed it up Tumour suppressor (anti-proliferation) genes slow it down Cancer, uncontrolled cell division, can result from too much speeding or too little slowing. GENE MUTATIONS When proto-oncogenes become mutated they are called ONCOGENES. An oncogene is similar to its non-mutated counterpart, but it is more active or produced in an unregulated way. ONCOGENES STIMULATE CELL DIVISION Extension material TUMOUR SUPPRESSOR GENES & CANCER Tumour suppressor genes (antiproliferation genes) suppress cell division They can also become mutated Causing uncontrolled cell division Animation GENETICS OF CANCER Cancers due to oncogenes only require mutation in one copy of the gene (the mutated version has dominance heterozygotes get cancer). Cancers due to antiproliferation gene mutation require mutation in both copies (the mutated versions are recessive homozygotes get cancer). CANCER TREATMENTS Surgery physical removal of cancer cells Radiotherapy damages DNA, killing cell Chemotherapy often inhibit aspects of cell cycle, killing cell. Rapidly dividing cells are more severely affected than slow dividing cells, so cancerous cells can be killed whilst limiting damage to less rapidly dividing cells (side effects) PACLITAXEL blocks a cell's ability to break down the mitotic spindle during mitosis COLCHICINE Inhibits the development of spindles as the nuclei are dividing. VINBLASTINE bind to tubulin, thus preventing the cell from making the spindles Web Sites http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv .View..ShowSection&rid=gnd.section.99 http://www.biology.iupui.edu/biocourses/N100/2k4 ch8mitosisnotes.html http://www.cancerquest.org Cell cycle and DNA content Advanced Higher paper Section B Q1 - 2002 a) M check point events triggered (1): anaphase is triggered following the M checkpoint, i.e. the spindle fibres contract and the chromatids migrate to opposite poles within the cell (1) b) Calculate the mitotic index (1) Table 1 the mitotic index is obtained by adding together the percentage of cells in the 4 stages of mitosis, or subtracting the percentage in interpahse from 100%; 100-87.3 = 12.7% (4.4 + 4.5+ 0.8 + 3.0 = 12.7%) (1) c) (i) Proteins involved in microtubule formation (1) Tubulin: (ii) Role of micortubules (1) Spindle fibre formation: (iii) Cell structure anchored (1) microtubule organising centre / centrosome d) Use Figure to show timing of cytokinesis relates to mitosis (2) cytokinesis is initiated at 57 minutes following the onset of prophase and starts 2 minutes after the start of anaphase (1). It finishes 1 minute following the end of telophase, 80minutes following the onset of mitosis (1). e) Percentage of cells at each stage indicative of time cells spend in each stage (2) Duration of prophase and metaphase are similar at around 27 minutes and 28 minutes respectively and comprise 34% and 36% of cells found in each stage respectively. Anaphase lasts 5 minutes, which is between 1/5th and 1/6th of the first two stages. Anaphase cells make up 6% of the cells in mitosis, which is exactly 1/6th the percentage in metaphase (and a bit less than 1/6th those in prophase). Telophase lasts 19 minutes or approximately 1//3rd the length that anaphase lasts and accounts for 4 times the percentage of cells in anaphase Alternative answer: Stage Duration (minutes) Percentage cells Ratio Prophase 27 34 27/34 = 0.79 Metaphase 28 36 28/36 = 0.78 Anaphase 5 6 5/6 = 0.83 Telophase 19 24 19/24 = 0.79 (1) The calculated ratios are in close agreement indicating that the percentage of cells in each stage is a good indicator of the time spent in each stage. (1) The calculated ratios are in close agreement indicating that the percentage of cells in each stage is a good indicator of the time spent in each stage. (1) f) Questions on Figure 2: (2) (i) DNA is synthesised during the S– phase of the cell cycle (1) (ii) Region C is when the relative amount of DNA is twice compared to region A. This must therefore be a phase when the chromosomes have been replicated i.e. following S phase = G2 and M. N.B. Cytokinessis is a separate stage from mitosis. (1) g) Proliferation gene that promotes tumour formation (1) Oncogene (proto oncogene is the unmutated version and refers to a protein involved in regulating cell division) (1) h) Effect of tumour promoting genes on cell division (2) Tumour promoting gene increases the percentage of cells undergoing cell division from 12.7% in unaffected cells to 57.1% in affected individuals (1). The tumour promoting gene alters the percentage of mitotic cells found in ineach phase suggesting it is changing the time spent in each phase (1). i) Use percentage values The numbers of cells counted in table 1 was different than the number counted for table 2 (1058 vs. 140 resp.) so a valid comparison is only possible through the use of percentages