Modeling and analysis of the latent period of osteosarcomas induced by incorporated239Pu: The role of immune responses

This paper considers the utility of a stochastic model of carcinogenesis, proposed earlier by Yakovlev and Polig, in quantitative analysis of the incidence of radiation-induced osteosarcomas in beagles injected with various amounts²³⁹Pu. The original version of the model failed to provide a good fit to our experimental data. The model has been generalized by incorporating a simple mechanism of lesion elimination, which is likely to be mediated by the immune system. Two versions of the model were developed: the first version (Model 1) assumed malignant cells to be a target for the immune attack, while in Model 2 initiated cells were assumed to be such a target. Model 2 was rejected by the likelihood ratio test, thereby indicating that the competing model provides a more plausible explanation of the experimental data. Since in experiments with incorporated radionuclides the dose rate varies with time, dose-rate effects cannot be observed directly and one must rely on mathematical models. The results of our numerical experiments show that, depending on the time of observation, both the direct and the inverse dose-rate effects may manifest themselves even at a fixed total dose level.