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CARCINOGENESIS

CARCINOGENESIS. Cancer = Malignant Tumour (Generic Term). Professor C.E. Connolly. Carcinogen An agent that induces cancer in a cell or group of cells Carcinogenesis The process of inducing genetic mutations in a cell i.e. Transformation i.e. permanent genetic damage. Oncogene

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CARCINOGENESIS

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  1. CARCINOGENESIS Cancer = Malignant Tumour (Generic Term) Professor C.E. Connolly

  2. Carcinogen An agent that induces cancer in a cell or group of cells Carcinogenesis The process of inducing genetic mutations in a cell i.e. Transformation i.e. permanent genetic damage

  3. Oncogene Is an abnormal or activated proto-oncogene which is a gene that normally controls cell proliferation GeneOncoprotein Growth Factors   GeneOncoprotein Growth Factor Receptors   GeneTyrosine KinasesCell (Oncoprotein) Proliferation   GeneOncoprotein Nucleus DNA    (c-myc)

  4. Carcinogen An agent which can induce neoplasia Types of Carcinogen Lung Cancer Tobacco Smoke Bladder Cancer Esophageal cancer 1. Chemical Asbestos Dust Lung Cancer Mesothelial Cancer Ionising Radiation Thyroid Cancer 2. Physical Leukaemia Non-ionising Radiation Skin Cancer Melanoma Papilloma Virus Cervix Cancer 3. Viral Epstein Barr Virus Lymphoma

  5. CarcinogenesisUV X-Rays 1. InitiationMutation Chemicals Hereditary 2. Promotion (Promoters) Proliferation of clone of mutated cells derived from the parent cell(s) Examples Hormones Estrogens Breast Cancer Endometrial Alcohol Liver Cancer + Hepatitis B/C Alcohol + Smoking- Cancer Mouth Cancer Larynx CancerEsophagus Malaria + Epstein Barr Virus  Lymphoma

  6. Carcinogenesis is a multi-step process with multiple sequential “hits” to the D.N.A. molecule. This results in either :- Activation of an oncogene which stimulates cell cycle turnover. OR Deletion of a gene or one half of gene (allele) causing it to malfunction so that the cell cycle is no longer held in check -: A tumour suppressor gene.

  7. Classification of Carcinogens Physical Ionising Radiation U.V. Radiation Electromagnetic Radiation Chemical Tobacco Smoke (Aromatic Hydrocarbons) Asbestos Nitrosamines (git) Viral DNA Viruses Papilloma Virus Epstein Barr H.B.V. RNA H.T.L.V.I. ? H.I.V.

  8. Chemical Adducts A carcinogen like Benzpyrene can combine directly with the DNA molecule – Intercalate – and cause oxidation of a base i.e. Guanine whose electrons are more loosely bound than the other bases. Oxidised Guanine reacts with H20) OXO-G combines with Adenine instead of Cytosine =Mutation!

  9. Now known that oxidative damage to a base can hop from base to base via an electric current i.e. the DNA molecule acts as a conductor! When an adduct is present to steal electrons. Adduct Guanine (-e) Guanine (Oxidised) (-e) Guanine (Oxidised) (-e) (Strand) Break Guanine

  10. DNA Damage • High Energy X-Rays or (gamma) Rays • High Energy U.V. Light • Products of Metabolism of Cell Free Radicals & Reactive O Species (Extra electron in outer shell)

  11. U.V. LightX-Rays SkinThyroid Bone Marrow Lung / Cervix Chemicals Smoking (Benzpyrene) Asbestos

  12. CELL CYCLE STIMULATION

  13. TERMINOLOGY 1. Carcinoma in Situ (Early) Definition: Carcinoma which has not broken through the basement membrane. • Dysplasia A premalignant change in an epithelium – enlargement of nuclei, prominence of nucleoli and loss of the normal architecture. • Metaplasia Change of one type of epithelium with another ie. Glandular --- squamous lung

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