Mathematical models and the statistical analyses of cell transformation experiments.

Statistical methods are developed and applied to the fitting of the one-hit curves to chemically induced transformations in Syrian hamster colonies. Data from several experiments in two laboratories are shown to fit the model well at all but the highest doses of benzo(a)pyrene. The ratio of the estimated parameters of the one-hit curves ("transformicities") is proposed as a measure of the enhancement by X-irradiation. Statistical tests for possible nonrandom variation among dishes are developed for the situation where a sample of dishes is used to estimate the total number of surviving cells. The methods of fitting and estimation are also extended to this case. Further analyses exclude selection as an explanation for the observed increase in transformation frequency with increased carcinogen concentration. The reproducibility of the fit of the one-hit model and the radiation enhancement measures is ascribed to the uniqueness of this in vitro system in which the direct target cell-insult interaction is not modulated by host intervention.