The aim of this project was to develop the stochastic models of tumorigenesis to investigate the implications of experimental data on tumour induction in wild type and p53 deficient mice for tumorigenesis mechanisms. These studies have focused on the development of stochastic process models for p53 mediated spontaneous and radiation- induced tumorigenesis in mice, in which up to 3 stages are assumed to be required for malignant transformation. The stages are conceived as the inactivation of one and both p53 alleles with a third, genetically unspecified stage which may be composite. The model has been used to explore the influence of mutation rate, stage number, and the number of stem cells at risk on the kinetics of spontaneous appearance of tumours and tumour multiplicity. As expected, tumours tended to occur earlier and the more tumours per mouse tend to be acquired with lesser stage number, higher mutation rate and higher stem cell number.
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Stochastic Modelling of Tumorigenesis in p53 Deficient Transgenic Mice