Application of Two- and Four-Mutation Carcinogenesis Models to UV induced Skin Tumours in Mice
Toepassing van twee- en vier-mutatiecarcinogenesemodellen bij door UV geinduceerde huidtumoren in muizen
Venema LB , Leenhouts HP
RIVM Report 610065005
This report contains the results of an analysis of the incidence of skin tumour in mice after exposure to ultra-violet radiation (UV). Two model types based on the multi-stage character of the carcinogenesis process were used: a two- and a four-mutation model. The mutation rate, the UV sensitivity and various other parameters were varied to fit the models to the experimental data. A computer programme was used to find the best solution in terms of maximum likelihood and the uncertainties in the various parameters. Two exposure types were used to test the models: lifetime exposure to various UV levels and short term exposures. The fits to only the life time exposure data indicate that the best results are found for a two-mutation model combined with a mutation rate proportional with the exposure squared, or a four-mutation model combined with a mutation rate linearly proportional with UV exposure. No difference in radiation sensitivity of the various mutation steps could be found. However, when also the short term exposure data were included in the analysis, different mutation sensitivities were found for the mutation steps. The results are discussed in relation with their relevance for the estimation of UV risks of low exposures. The results indicate a UV risk proportional with about the fourth power of UV exposure. A brief comparison is made with other analysis methods.