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Test 2 Review (Chemical Carcinogens (Initiating agents (capable only of…

- - - - Chemical carcinogen interacts with DNA and causes a mutation
      - Involves carcinogen metabolism, DNA damage, and cell replication
      - Only needs one exposure to induce mutation
      - Irreversible
      - Adduction of carcinogen with DNA, cell, replication, and fixation of mutation
        
        Phenotypically "normal epidermis"
    - - Clonal expansion of initiated cell
      - Nongenotoxic mechanisms
      - Reversible
      - Dose-dependent
      - Typically requires multiple exposures
      - Possible mechanisms of tumor promotion
        
        selective induction of proliferation
        
        immunosuppression
        
        oxidative stress
        
        decreased apoptosis
        
        methylation alteration
      - Expansion of initiated cells
        
        Altered gene expression/ enzyme activities
        
        Angiogenesis
        
        Altered differentiation
    - - additional mutations occur in initiated cell
      - tumors get ability to invade and establish distant metastases
      - irreversible
      - can require single or multiple exposures
      - Additional genetic events occurring
        
        Further alteration in differentiation
        
        Invasion
        
        Metastasis
  - - - Initiated cell
        
        Promotion - proliferation
        
        Benign tumor
        
        Progression - mutation, invade and spread
        
        Malignant tumor
- - - - Friends, turns off gene proliferation
      - Alterations could inactivate tumor suppressors
    - - Foes- tell cells to divide
      - Protooncogenes: code for growth factors/receptors, signaling proteins
      - Normal genes that can be activated to oncogenes by mutational events
      - Induce malignancy of a tumor cell through unregulated control of cell growth