Using a stochastic model to analyze the sequence of phenotypic changes in rat liver focal lesions

It is undisputed that carcinogenesis is a multistage process leading from normal cells to overt carcinoma. In the past, this theory has been described mathematically by multistage models made up of a number of compartments representing independently acting cells in the various stages of the carcinogenic process. Recently, a simple model has been formulated which describes the formation of hepatocellular focal lesions and their change to a more malignant phenotype on the basis of the entire clonal colony of cells rather than single cells as in the multistage models. This manuscript describes the use of this model to test the ordering of the sequence of phenotypes that have to be passed through on the way to malignancy.