CARCINOGENESIS

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CARCINOGENESIS

• Cancer Malignant Tumour
• (Generic Term)

Professor C.E. Connolly
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• 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

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• 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) Prolif
  eration ? ?
• Gene?Oncoprotein ?Nucleus DNA ? ? ?
• (c-myc)

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• 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

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• Carcinogenesis UV
• 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

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• 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.

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• 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.

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• 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!

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• 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

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• 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)

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• U.V. Light X-Rays
• Skin Thyroid Bone Marrow
• Lung / Cervix
• Chemicals
• Smoking (Benzpyrene)
• Asbestos

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CELL CYCLE STIMULATION
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• 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