Assays for Photocarcinogenesis: Relevance of Animal Models

Abstract

In the three and a half decades since the first published reports of squamous cell carcinomas in the skin of hairless mice exposed to ultraviolet radiation, this animal model has been developed and utilized extensively in basic and applied photobiology. Quantitative aspects of photocarcinogenesis had been investigated initially in haired mice; subsequently, the discipline of photoimmunology has developed largely on the basis of information derived from haired animals. Classical selective breeding methods, a few fortuitous mutations along the way, and the advent of genetic engineering have all enhanced the utility of the laboratory animal models. The benefits have included advances in our understanding of many influences on photocarcinogenesis such as genetic diversity, animal age, epidermal DNA damage and repair, wavelength dependency (action spectrum), ultraviolet radiation dose and its delivery, interactions with chemicals, and nutrition. As in other fields of basic and biomedical research, photobiological data have not been considered journalistically newsworthy or particularly contentious until they acquired potential economic impact. Thus, photocarcinogenesis became a more familiar word (at least along the Washington Beltway) when stratospheric ozone first appeared to be threatened by chlorofluorocarbons, and trends in photocarcinogenesis seemed less arcane when it appeared that the trends might be modified by consumer products and pharmaceuticals. The greatest challenge has not been in finding imaginative ways to exploit the models and to push the frontiers of science, but rather has been the uncertainty about quantitatively extrapolating the findings to humans. Research models would hardly be useful if they were not different from people (i.e., smaller, quicker to respond, shorter lived), and that fact encompasses differences in anatomy, physiology, metabolism, surface-to-weight ratios, etc. Selected examples from photomedicine (e.g., chronic solar damage, occupational exposure to tar, psoriasis phototherapy) tend to confirm that several basic principles about photocarcinogenesis are shared by man and mouse; other risk assessments await development and refinement, or remain to be corrected by experience.