Application of Two- and Four-Mutation Carcinogenesis Models to UV induced Skin Tumours in Mice
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Series / Report no.
Open Access
Type
Report
Language
en
Date
1995-12-31
Research Projects
Organizational Units
Journal Issue
Title
Application of Two- and Four-Mutation Carcinogenesis
Models to UV induced Skin Tumours in Mice
Translated Title
Toepassing van twee- en
vier-mutatiecarcinogenesemodellen bij door UV geinduceerde huidtumoren in
muizen
Published in
Abstract
Dit rapport bevat de resultaten van de analyse van de
incidentie van huidtumoren bij muizen na blootstelling aan ultra-violette
straling (UV). Twee soorten modellen, gebaseerd op het meerstadiumkarakter
van het carcinogenese proces, werden gebruikt om de incidentie te
beschrijven: een twee-mutatie en een vier-mutatie model. De
mutatiesnelheid, de gevoeligheid voor UV en verschillende andere parameters
werden gevarieerd om de modellen aan de experimentele resultaten aan te
passen. Een computerprogramma werd gebruikt om de beste aanpassing in
termen van de maximale waarschijnlijkheid te zoeken en de onzekerheid in de
verschillende parameters te schatten. Twee soorten blootstelling werden
gebruikt om de modellen te testen: langdurige UV-niveaus gedurende het
gehele leven en kortdurende blootstellingen. De analyses van alleen de
langdurige blootstellingen geven aan dat de beste resultaten gevonden worden
voor een twee-mutatie model met een kwadratische afhankelijkheid van de
mutaties voor UV, of voor een vier-mutatie model met lineaire gevoeligheid
van de mutaties voor UV. Een verschil in de gevoeligheden van de
verschillende mutaties onderling kon niet gevonden worden. Wanneer echter
ook de kortdurende blootstellingen worden meegenomen, is er wel significant
verschil in de gevoeligheden van de verschillende mutatiestappen. De
resultaten worden besproken op de relevantie voor schatting van de risico's
voor UV op huidtumoren. De resultaten geven aan dat voor lage UV-exposies
een verhoging van de risico's voor huidtumoren evenredig met ongeveer de
vierde macht van de UV exposie kan worden verwacht. Een korte vergelijking
wordt gemaakt met andere analysemethoden.
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.
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.
Description
Publisher
Leenhouts HP
Sponsors
RIVM
EU