Promotion

• • caused by the exposure of the initiated cell to a promoter, even after a delay of as long as 1 year
  • involves the selective clonal expansion of initiated cells to produce a preneoplastic lesion
  • Non genotoxic
• • Promotion is a slow process
  • exposure to promoter must be sustained for a certain period of time (repeated applications/ continuous exposure)
  • dose dependent, threshold and reversible
  • usually organ specific
• • Tumor promoters modify gene expression --> increases cell proliferation and/or inhibit apoptosis of the initiated cell
• Promotor

  • Substances that mediate their effect through epigenetic changes (non-genetic changes); interacting with elements of signal transduction pathways, altering regulation --> uncontrolled proliferation of initiated cells
  • not carcinogenic or mutagenic
• Promoter

  • must be given after an initiator, and requires prolonged exposure to cause tumor formation
  • promoter alone/ a promoter preceding an initiator does not result in cancer
• Mouse Skin Studies

  • Initiator alone = very few tumors produced
  • Initiator --> Chronic treatment with a tumor promoter (1 week - 1 year) = produced many tumors
  • Order of the treatment is critical; Initiator must be given first
  • Chronic treatment with promotor w/o initiator = very few tumors
  • Promotion: Reversible in early stages; e.g. equal number of promoting doses are administered but the doses are spaced further apart in time = tumors would not develop/ would be greatly diminished in number