Progression: accumulation of additional irreversible genetic changes; marked by increasing genetic instability + malignancy
Initiation to promotion
The initiated tumor cells may remain dormant (not undergo clonal expansion) for a long period of time before it becomes a tumor through cell proliferation in the presence of promoters
The dormancy is probably due to the suppressant influence of the surrounding normal cells exerted through certain intercellular communication
The suppressant influence can be reduced by:
Growth factors (e.g., Phorbol esters)
Cell killing (e.g., Cytotoxic chemicals)
Inhibition of gap junction intercellular communication (e.g., DDT and phenobarbital)
Changes in DNA methylation profile
Initiation (Genotoxic): Formation of DNA adducts on proto-oncogenes and/ or tumorsuppressorgenes --> Mutation
Promotion (Non-genotoxic): Increase cellproliferation, Inhibit intracellularcommunication, DNA methylation profile
Progression: Additional genetic and epigenetic changes --> Genomic instability