Overview of Cancer PDF

Overview of Cancer DR.HAROON HABIB, PH.D ALA-TOO INTERNATIONAL UNIVERSITY  What is cancer? A general term for more than 100 diseases characterized by abnormal and uncontrolled growth of cells. What cancer is not Cancer cells are not immortal cells. ...

Overview of Cancer DR.HAROON HABIB, PH.D ALA-TOO INTERNATIONAL UNIVERSITY  What is cancer? A general term for more than 100 diseases characterized by abnormal and uncontrolled growth of cells. What cancer is not Cancer cells are not immortal cells.  Cell lifespan Typical cells live ~ 40 generations. Afterwards, cells build-up excessive genetic errors that it results in death. Cancerous cells live longer, resulting in greater probability of error accumulation.  Cancer Terms Benign tumor – A non invasive growth with the potential to become malignant. Malignant tumor – When a cancerous cells spread to other parts of the body via the bloodstream/lymph nodes Mutagens vs. Carcinogens Mutagens are any substance that cause alterations in genetic material. Does cancer occur without a mutation? - No Does mutation occur without cancer? - Yes  Types of Mutations Point Mutations – Replacement of one nucleotide with another.  Types of Mutations Frameshift Mutations – Deletion of nucleotide(s).  Types of Mutations Chromosome deletions Thymine dimers – UV light Strand breaks – X-rays, ionizing radiation DNA adducts – carcinogens Oxidized base – oxidizing agents Mutagens vs. Carcinogens Carcinogens are compounds that induce serious mutations to DNA that can lead to cancer.  Mutagen Screening: Ames Test : Salmonella typhimurium Reverse mutation test. Mutant bacteria that requires histidine to grow. Mutation is from a single nucleotide. Expose bacteria to potential mutagen and grow on a plate without media. Mutagens will randomly reverse the original mutation, allowing bacteria to grow without histidine.  If bacteria grow = compound is mutagenic If bacteria does not grow = non- mutagenic Common Exposures to Mutagens and Carcinogens Polycyclic aromatic hydrocarbons (PAH) - burning fossil fuels Why are my hot dogs always pink? - creosote-soaked Nitrosamines wood - Meat (woodpreservatives pilings) - Saliva  Common Carcinogenic Exposures Benzo[a]pyrene (PAH) Results from incomplete combustion of organic compounds. Found in cigarette smoke, car exhaust, forest fires, food.  Common Genotoxic Exposures Heterocyclic Amines (HCA) Known to cause cancer in animal studies. Produced from the cooking process of animal tissue above 180 degrees C. Higher temperatures produce more HCA  Flame cooked meats Bake (350F) = 176 C (exterior only) Deep fry (400F) = 232 C Flame BBQ (800F) = 426 C HCA Formation from High Temperature Cooking  Commonly Genotoxic Exposures Acrylamide Found to be genotoxic in in vitro tests. Produced from high temperature cooking of starchy foods: french fries, potato chips.  Common Carcinogen Exposures Alcohol and Smoking – Synergistic effect. - Alcohol dissolves fats in membranes. - Carcinogens in smoke enters cells more easily  increases damage potential. = carcinogen  Bioactivation Compounds are more toxic after being metabolized. Ex: Benzo[a]pyrene Metabolism occurs via cyp450’s in Phase I and Phase II reactions (multifunctional oxidases) Bioactivation Mutagenicity Test  Teratogens Teratogens are compounds that are genotoxic only to developing fetus. Mother is unaffected. Thalidomide – Used as a sedative to combat nausea in pregnant women in 1950’s. Caused massive developmental defects through genetic toxicity.  Molecular Cancer Progression Model Looks at the types and secquences of DNA change leading to cancer Clinical Cancer Progression Model Looks at the cell/tissue morphology, cell growth rate  Clinical Cancer Patterns Recurrence of cancer often occurs after the growth has been surgically removed. In 70% of recurrence cases, cells will dediffferentiate to indicate recurrence. In 30% of recurrence cases, cells will appear perfectly normal, then suddenly become cancerous. Molecular Patterns in Cancer Cancer can arise from multiple gene mutations for: DNA repair Anchorage dependence Growth suppressors Growth promoters P53 (apoptosis gene) Molecular Patterns in Cancer Specific sequences of gene loss are commonly (not always) found in cancer. DNA repair – first P53 (apoptosis gene) – first Growth suppressors - second Growth promoters - second Anchorage dependence - last  Patterns of Cancer Multiple combinations of gene loss can all result in cancer. Cancer at the same site (lung) in two individuals often have a different molecular basis. No such thing as a universal cure for cancer. Environmental Toxicologists  Initiation Initiation Generates an neoplastic cell Chemical + DNA = mutation – DNA repair – Apoptosis (cell death) – Nothing Permanent in the genome (mutation is irreversible) Gene expression A neoplastic cell Initiation may never develop into cancerous growths  Promotion Neoplastic cell grows – Possibly after a latent period – Slow process, – Repeated exposures Benign tumour Dysplasia DNA repair mechanisms are damaged. Cells still appear normal but increased DNA mutations occur.  Progression Begins with visible tumour Continued alteration of genetic make-up of the cell Invasion to adjacent tissues Metastasis to unrelated organs via blood/lymph Malignant tumour Hyperplasia Cells lose ability to communicate chemically with each other. Other cancer models  Problems with research Latency 10-20 yr No safe dosage Satisfying all models Cure vs prevention Cure vs. Prevention End of lecture