[Frontiers in Bioscience 7, d752-764, March 1, 2002]
PHYSICAL VARIABLES IN EXPERIMENTAL PHOTOCARCINOGENESIS AND QUANTITATIVE RELATIONSHIPS BETWEEN STAGES OF TUMOR DEVELOPMENT
Frank R. de Gruijl 1 and Jan C. van der Leun 2
1Dermatology, Leiden Univ. Med. Ctr./LUMC, Sylvius Lab., Wassenaarseweg 72, NL-2333 AL Leiden, Netherlands, 2 EcoFys, PO Box 8408, NL-3503 RK Utrecht, Netherlands
TABLE OF CONTENTS
Solar ultraviolet (UV) radiation is a prominent environmental carcinogen, but it does not penetrate any deeper than the skin. The UV-related skin cancers are by far the most common form of cancer among white Caucasians in the USA and Australia, and this poses a serious public health problem. Chronic UV exposure of hairless mice is a well established model for squamous cell carcinomas in man. It is important to identify the essential physical variables, and explore fully how photocarcinogenesis evolves in dependence of these variables. The 3 main physical variables in photocarcinogenesis are (i) the wavlength of the radiation, (ii) the exposure and (iii) time. A good quantitative description of tumor induction and precursing stages can be given in terms of these variables. An analysis of this description shows us that the early induction of clusters of epidermal cells that over-express mutant p53 ('p53 patches') are closely and, most likely, causally linked to the eventual tumors. These p53 patches may thus serve as early indicators of tumor risk. The induction of an immune-tolerance toward the UV-induced tumors precedes the actual occurrence of the tumors at high daily doses, but extrapolation indicates that this order of events may be reversed at low daily doses. This disparity between the dose-time relationships for the tumor tolerance and the tumors needs to be investigated further. It could imply a shift to non-immunogenic tumors at low daily doses.