Analysis of lung tumour risk in radon-exposed rats: an intercomparison of multi-step modelling

Three carcinogenesis modelling groups have both jointly and separately appl ied a multi-step carcinogenesis model with clonal expansion to one data set of lung tumours in rats exposed to radon (CEA, France). This study was des igned to investigate the differences in modelling approach and fitting proc edures used by the three groups in detail, and to explore possible discrepa ncies in the results. Using the same model assumptions and a (linear) radia tion dependence on the first model step only, the three groups arrived at i dentical best fits, proving that the mathematical formalisms and fitting pr ocedures do not lead to different results. However, when each group was all owed to find its own preferred fit for this data set, all three found a sig nificantly better, but different fit to the data. All solutions indicated r adiation to be an initiating agent and found additional radiation action ne cessary. The character of this additional radiation dependence, however, co uld not be unambiguously pinpointed. Tumour incidence data were described e qually well when radiation dependence was taken into account in clonal expa nsion ("promotion") or in the second mutational step ("transformation"); ex tension to three model stages also resulted in an adequate description. The study showed that, although the three groups used one carcinogenesis model in principle, different model assumptions and/or different methods of find ing the "best fit" could result in different descriptions of experimental d ata. This implies that on statistical grounds, different interpretations ca n be given for the action that radiation had in this data set. Different da ta, i.e. other data sets with age-dependent tumour data and/or information from cellular radiobiology experiments, are needed to specifically pin down the radiation dependence in the multi-step carcinogenesis process.