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Stochastic Analysis of Intermediate Lesions in Carcinogenesis Experiments

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  • E. Georg Luebeck
  • Suresh H. Moolgavkar

Abstract

In many animal model systems for carcinogenesis, well characterized putative premalignant lesions are observed. A much studied example is provided by the enzyme altered foci in rodent hepatocarcinogenesis experiments. In a recent paper, we proposed a method for the quantitative analysis of such premalignant lesions. The model used in that paper assumed that the mean growth of premalignant clones is exponential. However, it has been suggested that such a model is oversimplified. In this paper, we relax the assumption of exponential mean growth. The new model contains one extra parameter that measures departures from exponentiality. Use of the model is illustrated by analysis of ATPase deficient foci in the liver of rats given NNM (N‐nitrosomorpholine) in their drinking water. The analysis suggests that the clonal growth of altered cells is significantly accelerated (superexponential) for nontoxic doses of NNM. Finally, the hazard function of the two‐mutation model for carcinogenesis is briefly discussed under nonexponential (mean) growth of intermediate cells.

Suggested Citation

  • E. Georg Luebeck & Suresh H. Moolgavkar, 1991. "Stochastic Analysis of Intermediate Lesions in Carcinogenesis Experiments," Risk Analysis, John Wiley & Sons, vol. 11(1), pages 149-157, March.
    • Handle: RePEc:wly:riskan:v:11:y:1991:i:1:p:149-157
    DOI: 10.1111/j.1539-6924.1991.tb00585.x
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    Cited by:

    1. Anup Dewanji & Jihyoun Jeon & Rafael Meza & E Georg Luebeck, 2011. "Number and Size Distribution of Colorectal Adenomas under the Multistage Clonal Expansion Model of Cancer," PLOS Computational Biology, Public Library of Science, vol. 7(10), pages 1-10, October.
    2. Wolfgang F. Heidenreich, 2005. "Heterogeneity of Cancer Risk Due to Stochastic Effects," Risk Analysis, John Wiley & Sons, vol. 25(6), pages 1589-1594, December.
    3. Claire D. Sherman & Chnstopher J. Portier, 1998. "Eyes Closed: Simple, Intuitive, Statistically Sound, and Efficient Methods for Estimating Parameters of Clonal Growth Cancer Models," Risk Analysis, John Wiley & Sons, vol. 18(5), pages 529-534, October.
    4. Suresh H. Moolgavkar, 1994. "Biological Models of Carcinogenesis and Quantitative Cancer Risk Assessment," Risk Analysis, John Wiley & Sons, vol. 14(6), pages 879-882, December.
    5. David A. Kramer & Rory B. Conolly, 1997. "Computer Simulation of Clonal Growth Cancer Models. I. Parameter Estimation Using an Iterative Absolute Bisection Algorithm," Risk Analysis, John Wiley & Sons, vol. 17(1), pages 115-126, February.

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