Two Mutation Model for Carcinogenesis: Relative Roles of Somatic Mutations and Cell Proliferation in Determining Risk

  • Suresh H. Moolgavkar
  • Georg Luebeck
  • Mathisca de Gunst


Two experimental data sets are analyzed within the framework of a two-event model for carcinogenesis. In the first, the number and size distribution of altered hepatic foci, which are thought to be premaligant lesions, are analyzed as functions of dose of an administered agent (N-Nitrosomorpholine, NNM). Definitions of initiation and promotion potencies are proposed. Results of the analysis indicate that NNM is a strong initiator and a weak promoter. In the second, the time to appearance and the probability of malignant lung tumors in rats exposed to radon are analyzed as functions of total exposure and rate of exposure. The results indicate that fractionation of exposure increases the lifetime probability of tumor, and that the efficiency of fractionation can be explained by the relative effects of radon daughters on the mutation rates and the kinetics of growth of initiated cells.


Total Exposure Exposure Rate Intermediate Cell Radon Exposure Lifetime Probability 
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Copyright information

© Birkhäuser Boston 1990

Authors and Affiliations

  • Suresh H. Moolgavkar
  • Georg Luebeck
  • Mathisca de Gunst

There are no affiliations available

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