Multistage carcinogenesis modeling and the initiation event.

Carcinogenesis is generally considered to be a multistage process classified under "initiation," "promotion," and "progression," and it is therefore of interest to know how radiation might affect them. Models which are currently being used with some success to analyze a variety of data are based on the two-mutation with clonal expansion model developed by Moolgavkar and Knudson [J Natl Cancer Inst 66:1037-1052, 1981]. These models imply that the "initiation" event would be a mutation but also imply that "progression" also involves mutation and that both these events could be influenced by radiation. The models offer the possibility of calculating the incidence of cancer over lifetime and can simultaneously provide the age and dose dependence of cancer. The models have implications for radiation protection and imply that radiation risk is related to spontaneous cancer incidence and that spontaneously induced "initiation" may also be associated with radiation-induced cancer.