Development of skin tumors in hairless mice after discontinuation of ultraviolet irradiation.

The development of skin tumors (mainly squamous cell carcinomas) in hairless Skh-HR1 mice after discontinuation of a course of daily UV irradiations (wavelengths, 280-370 nm) is compared to that when the daily irradiations are continued. Under conditions of continued daily exposures 50% of 22 animals contracted tumors with diameters of at least 4 mm in 135 days. With exposures stopped after 35 or 19 days (2 groups with 24 and 23 mice) this time interval increased to 280 and 645 days, respectively; the rate at which multiple tumors developed on the mice was correspondingly lower. A mathematical model, derived from a larger experiment (223 mice) with different levels of chronic UV exposure, successfully predicts the tumor development after discontinuation of UV exposure. This model is similar to those used in risk assessments for skin cancers in human populations, e.g., in relation to stratospheric ozone depletion, sunbeds, etc. The model separates UV-driven processes from purely time-dependent processes. These stochastic processes, described by Weibull statistics, form stages in the tumorigenesis. This interpretation of the data indicates that a late, UV-independent stage occurs between the smallest observable tumors and larger ones with diameters of over 4 mm. This could be a simple growth stage, but histopathology suggests that it may also entail a transition from actinic keratosis to squamous cell carcinoma.