Transcript Carcinogens
IN Question: 1. What are carcinogens? 2. Explain your answer. Carcinogen PPT Notes: (Due in 15 min.) • Get a computer and Log-In • Complete the notes using Course Weblinks Link to PPT called “Carcinogens” • Glue in ISN • Get Mrs. White’s Stamp/Initials • Pick-up & Finish in 30 min: Lab: Neoplasia’s of Organ Systems Carcinogens are… • Natural or synthetic compounds that cause genetic mutations that lead to cancer. • Found naturally and environmentally: Staging of Cancer Stage 0 Cancer not found in surrounding tissue – in situ Stage I Cancer found in surrounding tissue, no lymph node involvement Stage II Usually lymph node involvement Stage III Lymph nodes have clumped together and other lymph nodes are involved Stage IV Metastatic cancer – has spread beyond the primary site to other organs in the body Carcinomas, the most common types of cancer, arise from the cells that cover external and internal body surfaces. Lung, breast, and colon are the most frequent cancers of this type in the United States. Sarcomas are cancers arising from cells found in the supporting tissues of the body such as bone, cartilage, fat, connective tissue, and muscle. Lymphomas are cancers that arise in the lymph nodes and tissues of the body's immune system. Leukemias are cancers of the immature blood cells that grow in the bone marrow and tend to accumulate in large numbers in the bloodstream. Carcinogens-or, according to the National Toxicology Program, “reasonably anticipated to be a human carcinogen.” • 246 of these and still counting! • Benzene hexachloride – pesticide, liver cancer, nervous system dysfunction • Oxybenzone-sunscreen, hormone disruption, cancer of all kinds, especially melanoma and other skin cancers • Sunscreens-see attachment Etc…….. • Captafol – pesticide, all cancers, in water supplies, even though it was banned in 2006, but not in other countries • Nitrotoluene – paper mills, munitions factories, leach into water supplies, produce 10-50 million pounds a year in U.S. • Styrene – styrofoam containers • Hepatitis B and C – liver cancers Etc…. • Helicobacter pylor- stomach • Trichloroethylene-water and food • X-radiation and gamma radiation-differs by age: X-rays in children-leukemia; x-rays in women of childbearing age – breast and ovarian; later years – lung • Benzene – detergents, plastics, and dyes Etc…. • Sodium laurel and laureth sulfates-engine degreaser, concrete floor cleaner, builds up in body, uses in toothpaste causes enamel erosion that leads to cavities. Forms nitosamines • DEA(lauramide diethanolamine)Readily absorbed – in cosmetics and takes to all organs Etc…. • Sodium flouride • Propylene glycol • Formaldehyde – hair straighteners and baby shampoo • All these are implicated as mutagens and teratogens Aspartame Carcinogenesis – Overview • Agents Causing Neoplasia 1. 2. 3. 4. 5. 6. Chemical Oncogensis Radiation Oncogenesis Viral Oncogenesis Nutritional Oncogenesis Hormonal Oncogenesis Genetic Oncogenesis Carcinogenesis Agents Causing Neoplasm • Carcinogens – substances known to cause cancer or produces an increase in incidence of cancer in animals or humans – Cause of most cancers is unknown – Most cancers are probably multifactorial in origin – Known carcinogenic agents constitute a small percentage of cases – Unidentified ‘environmental’ agents probably play a role in 95% of cancers Carcinogenesis Agents Causing Neoplasm • 1 - Chemical Carcinogenesis – Types • Proximate or direct-acting : act locally without metabolic change • Indirect acting : carcinogenic only after being metabolised into active compounds (procarcinogen ultimate carcinogen) Carcinogenesis Agents Causing Neoplasm – Mode of carcinogenesis • Inducing changes in DNA – eg. Base alkylation, deletion, breakage, cross-linkage • Epigenetic mechanisms • Synergistic action with viruses • Promoter for other carcinogens – Difficulties in identifying carcinogen • Numerous industrial, agricultural, household chemicals present in low levels • Exposed to large number of chemicals in a lifetime • Long lag phase Carcinogenesis Agents Causing Neoplasm • 2 – Radiation Oncogenesis – Types of oncogenic radiation • • • • Ultraviolet X-ray Radioisotopes Nuclear Fallout – Mode of oncogenesis • Direct effect on DNA • Activation of cellular oncogenes Carcinogenesis Agents Causing Neoplasm – UV Radiation • Solar UV radiation associated with skin cancers – squamous CA, basal cell CA, malignant melanoma • Fair-skinned and elderly are susceptible • UV light is believed to induce cross-linkages between DNA molecules and CA occurs when repair mechanisms are not efficient Carcinogenesis Agents Causing Neoplasm – X-ray radiation • Earlier use of X-rays caused skin cancer, leukemia and papillary thyroid CA • Radiotherapy causes raditation-induced malignancy 10-30 yrs later – usually sarcomas • Diagnostic X-rays are considered to have no increased risk except in abdominal x-rays which increase incidence of leukemia in the fetus Carcinogenesis Agents Causing Neoplasm – Radioisotopes • Osteosarcoma common among factory workers who use radium-containing paints • Radioactive mineral mining in Europe and USA associated with lung cancer • Thorium increases risk of liver cancer – hepatocellular, angiosarcoma, cholangiocarcinoma • Radioactive iodine – increased risk of cancer 15-25 years later Carcinogenesis Agents Causing Neoplasm – Nuclear Fallout • Hiroshima, Nagasaki (atomic blasts) • Marshall islands (atmospheric testing of nuclear divide containing radioactive iodine) • Chernobyl, 1986 Carcinogenesis Agents Causing Neoplasm • 3 – Viral Oncogenesis – Types • Oncogenic RNA Viruses • Oncogenic DNA Viruses – Mode of Oncogenesis • RNA Virus • DNA Virus Carcinogenesis Agents Causing Neoplasm – Detection of viral genome • Identification of viral-specific nucleic acid sequences by hybridisation with DNA/RNA probes • Recognition of virus-specific antigens on infected cells • Detection of virus-specific mRNA Carcinogenesis Agents Causing Neoplasm • 4 – Nutritional Oncogenesis – Scant evidence linking cancer to diet except for known chemical carcinogens – Some associations • Low-fiber diet and colonic CA • Fatty diet with breast ca • Betel leaves with oral ca – Protective agents – ?antioxidant effect, awaiting confirmation • Beta-carotene • Vitamin C, E • Selenium Carcinogenesis Agents Causing Neoplasm • 5 – Hormonal Oncogenesis – Types • Induction of Neoplasms by Hormones • Dependence of Neoplasms on Hormones – Hormones inducing Neoplasms • Estrogen – breast ca • Diethylstilbestrol (DES) – vaginal and uterine ca Carcinogenesis Agents Causing Neoplasm – Hormonal Dependence of Neoplasms • Neoplasm not caused by hormones but depend on hormones for optimal growth • Neoplastic cells possess receptors for binding hormone • Loss of hormonal stimulation slow but does not halt growth • Examples – Prostate CA – Breast CA – Thyroid CA Carcinogenesis Agents Causing Neoplasm • 6 - Genetic Oncogenesis (Role of Inheritance) – Types • Mendelian inheritance • Polygenic inheritance • Association with inherited diseases – Mendelian Inheritance • Dominant • Recessive Carcinogenesis Agents Causing Neoplasm • Examples – Retinoblastoma – Wilm’s tumor – Others » Neurofibromatosis (type 1 von Recklinghausen’s disease) » Multiple endocrine adenomatosis (MEN) » Familial polyposis coli » Nevoid basal cell carcinoma syndrome Carcinogenesis Agents Causing Neoplasm – Association with Inherited Diseases • Many inherited diseases are associated with higher risk of neoplasia • Types : – Syndromes characterised by increased chromosomal fragility – Syndromes of immunodeficiency conclusion • Pathogenesis of cancer is complex • it is a genetic disease- either acquired genetic abnormality or inherited genetic abnormality • It arises when several mutations accumulate within genome Acquired environmental factors chemicals ,radiation ,viruses Changes in genome of somatic cells Activation of growth promoting oncogenes Genetic factors Inactivation of cancer supressor genes Expression all altered gene products and loss of regular gene products MALIGNANT NEOPLSM