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MUTATIONS / CANCER BIOLOGY 12 Mutations and Protein Synthesis MUTATIONS are any change in the original coding of DNA, causing a mutation in the gene. Not all gene mutations are negative. Without genetic mutations living organisms would not have evolved over time. Slight mutations are usually beneficial in order to adapt to an ever changing environment. Mutations and Protein Synthesis FRAMESHIFT MUTATIONS occur when a nucleotide (nitrogenous base) is deleted or one is substituted which will shift the codons. When this happens the order of amino acids are altered changing the final protein. Mutations and Protein Synthesis • There are three different types of point mutations. 1) Silent Mutations – occur when the DNA code has been changes however the same amino acid is still placed into the polypeptide chain. The gene is still expressed as a normal protein. NO NEGATIVE IMPACT ON PROTEIN. Mutations and Protein Synthesis 2. Nonsense Mutations: These are when the mutation results in the addition of a new nucleotide into the DNA. In the case of sickle cell anemia one nucleotide is changed which changes the amino acid. • Some can have very serious effects due to “Frame shifting” in all the mRNA codons that are down from the mutation, if there is a deletion or the addition of a nucleotide. 3. Missence Mutation: These are when a nucleotide is deleted or added and the result is a “STOP” or “ NONSENSE CODON, which prevents the formation of the complete protein. Sickle Cell Anemia Gene Control • The human genome contains hundreds of thousands of genes. • These determine all your genetic traits and control all your biochemistry. • A mutation can occur during replication however enzymes are used to check the bonding between nucleotides to ensure the correct order has occurred. Considering the number of times cells reproduce the number of mutations are minimal. MUTAGENS Mutagens are chemicals that cause a mutation in the sequence of DNA. Some mutagens are: 1.Asbestos 2.X-rays 3.UV radiation 4.Viruses 5.Benzene 6.Microwaves Cancer • Cancer is genetic control lost. • Specifically, cancer is a loss of a cells ability to control its own rate of mitosis. • This typically results from a mutation in the genetic control mechanism. Cancer Cancer isn’t a disease in the conventional sense because: 1. It isn’t caused by a specific pathogen (although viruses are suspect in some). 2. Cancer isn’t characterized by one set of symptoms. • In its simplest sense, cancer is rapid and uncontrolled cell growth. Cancer • The problem is that because these cells are reproducing so rapidly ( up to once every 3 hr,), they do not have a chance to differentiate and become useful. • They are like embryonic cells. • Despite being useless, they still must be fed and provided with the metabolites of life. Cancer • They survive at the expense of normal cells that do have a function. • This ultimately can lead to the death of the individual as so many normal cells become sacrificed to satisfy the voracious appetite of the cancer cells. Comparing Normal Cells and Cancerous Cells Cancer Characteristics of Cancer Cells 1. They lack differentiation 2. Have abnormal shaped nuclei 3. Lack contact inhibition 4. Don’t stick to each other, often migrate 5. Can stimulate vascularization. CONTACT INHIBITION • CONTACT INHIBITION in normal cells results when two cells grow toward one another they will stop growing. This is triggered by a growth factor (hormone) which switches the cells off. • CANCEROUS CELLS do not respond to this hormone and will continue to grow recklessly eventually taking over normal cells. These cells are like the “bully on the block” Stages of Cancer 1) Neoplasia: normal cell becomes cancerous 2) Anaplasia: growth of disorganized mass of cells - tumor 3) Angiogenesis (vascularization): stimulation of new blood vessel growth into tumor. 4) Metastisis: migration of cancer cells into circulatory and lymphatic systems How can we protect ourselves? Eat a well balanced diet, avoid fatty foods. Avoid UV radiation, use sun block. Protect lungs from harmful chemicals. Safe sex, avoid multiple partners and early sexual activity. Maintain a healthy immune system, rest and exercise boosts immune response. Reduce exposure to radiation (microwaves, X-rays) Early Warning Signs 1. abnormal bleeding 2. sores that will not heal 3. pesistent cough 4. abnormal discharge of fluids 5. localized pain 6. change in mole 7. dizziness, persistant headache, blurred vision 8. lump under skin 9. change in diet, loss of appetite How Cancer Begins 4 main causes of CANCER HEREDITY VIRUSES CHEMICALS RADIATION Initiation of Cancer Carcinogenesis: Carcinogenisis is the formation of cancer cells due to exposure to certain carcinogens. These carcinogens are agents like; chemicals like benzene, or various forms of radiation like UV rays. MUTATIONS may activate PROTO-ONCOGENS or inactivate tumor suppressor genes Cancer • A cancerous gene is called an “oncogene”. • Expression of these genes cause • uncontrolled cell growth. • These can be mutated from normal genes that control cell growth and cell division called “proto-oncogenes”. • A mutation can convert a proto-oncogene into an oncogene. Cancer • This will not necessarily result in cancer. • To manifest cancer, the protooncogene may need to be hit repeatedly by a “promotor”. • These promotors may be external things such as environmental irritants (smoke, chemicals, physical irritation) or internal thing such as growth hormones or growth factors. Cancer • Therefore, the proto-oncogene is converted to an oncogene by an initiator but must be activated to a cancer cell by promotors. • Learn and know the 7 warning signs of cancer. • Viruses have been implicated in certain cancers due to their ability to introduce new genes (such as an oncogene) or mutate a proto-oncogene. STEPS in CARCINOGENESIS Normal cells All normal cells have genes called proto-oncogenes on chromosomes. Therefore all cells can become cancerous. Step 1 INITIATION Step 2 PROMOTION Step 3 Proto-oncogenes oncogenes CARCINOGENESIS INITIATORS are; PROMOTORS are; 1. Viruses 2. Chemicals 3. Radiation 1. HP virus 2. benzene, asbestos 3. X-rays, microwaves UV radiation Cancer The Common Cancers 1. Lung Cancer 2. Breast cancer 3. Prostate cancer 4. Uterine (cervical) cancer 5. Colon cancer 6. Skin cancer Common Cancers • Melanomas; deadly skin cancers • Carcinomas; affect epithelial tissue ( breast and lung cancer) • Adenocarcinomas; glandular tissue ( ovarian and pancreatic cancer) • Sarcomas; affect conncective tissue ( bone cancer) • Lymphomas; affect lymph tissue ( spleen, certain white blood cells) • Leukemias; affect leukocytes (white blood cells) Skin Cancer Skin Cancer Colorectal Cancer