Abstract— Hairless mice were irradiated repeatedly by exposure to unfiltered black‐light (FR74T12 PUVA) fluorescent lamps and the time to development of skin tumors was determined. For several groups of animals the treatment variable was the size of the weekly dose. A similar approach had been used previously to determine dose‐response characteristics for other ultraviolet radiation emitting sources: a xenon arc solar simulator (with a series of five cut‐off filters producing five source spectra), and a fluorescent (FS40T12) “sunlamp”. The median tumor latent period (time period for just more than one half of the animals to develop at least one tumor each) was accurately predicted for all these ultraviolet radiation emitting sources by a mathematical equation incorporating the spectral source description and a spectral weighting function. The weighting function judged most appropriate for ultraviolet radiation‐induced photocarcinogenesis was the action spectrum, determined previously, for acute (single dose) skin edema in hairless mice. The mathematical equation assigns no effectiveness to wavelengths greater than 330 nm. There was no evidence for wavelength interaction in the spectral range of 26MW nm. Our data, combined with results of others, lead us to conclude that radiation with wavelength greater than 330 nm has an average relative efficacy (297 nm =1.0) less than 0.0002, and that this efficacy is not detectable with sources in which at least 2% of the UV radiation is in the UV‐B range.
Relevance of Animal Models of Photocarcinogenesis to Humans P. Donald ForbesArgus Research Laboratories, Inc.,* Horsham, PA, USA Ultraviolet radiation is a natural and variable component of our environment; its one unambiguous benefit is the vitamin D, production that it stimulates. Ultraviolet radiation is better known for the several types of skin damage it causes, including the production of skin tumors. Evaluating benefits and risks may thus be considered essential to the life of a cutaneous photobiologist. Like most organisms exposed to solar UV radiation, humans have an assortment of mechanisms that function to offer protection or to repair damage caused by UV radiation. Mechanisms for the production of damage, as well as for protection and repair, would be poorly understood were it not for the availability of laboratory animal models in research.This essay, along with others in the symposium proceedings, addresses the relevance of photocarcinogenesis research models to the human situation. To set the stage, we begin by considering the characteristics of the material selected for laboratory studies and the designs of such studies, whether for basic research or for purposes of regulatory submission. Mouse modelsAmong laboratory mammals, mice are particularly suitable for toxicology studies because they are prolific, and because their size facilitates their use in numbers appropriate for statistical power. Mice are thus the most used animals in experimental carcinogenesis. Their dense fur is, however, a disadvantage for photocarcinogenesis studies. The earliest laboratory studies on photocarcinogenesis depended on the exposure of repeatedly depilated skin, or of the more sparsely haired areas such as ears and extremities (1). The tumors that were produced included many that exhibited malignant $Argus Research Laboratories, Inc., is a member of the Genzyme Transgenics, Corp. family of companies.criteria but few that were morphologically similar to those found in human skin damaged by UV radiation. In addition, removing the hair in order to expose the underlying skin introduced an unmeasured stirnulatory effect on cell turnover, along with other confounding effects. The discovery of UV-induced squamous cell tumors in genetically hairless mice (23) was thus a pivotal laboratory finding.Genetically hairless mice had been known among mouse fanciers for the better part of a century, and the heritable characteristics of one recessive allele in particular (hrlhr) were described in detail in the 1920s (4). By the 1950s, breeding studies had resulted in the availability of this allele in a diversity of mouse stocks and strains, housed in universities, government laboratories, and research foundations (5). In general, the hairless stocks and strains were characterized by small litters and relatively inefficient output of the desired hairless phenotype (typically, heterozygous haired dams were used because the homozygous hairless dams successfully raised very few offspring). Exceptions to this rule were the animals repo...
New drugs undergo safety evaluations of many types. For some drugs, a photocarcinogenesis study forms one of the elements in the overall toxicology package. Photocarcinogenesis studies are designed to evaluate a drug's ability to modify the growth and development of ultraviolet radiation (UVR)-induced skin tumors in albino hairless mice. "Exposure control" groups in such studies receive the UVR, either alone, or in combination with the "vehicle" or carrier associated with each study. This report presents skin tumor data from control groups compiled from nine consecutive studies conducted at this testing facility. The endpoints evaluated included median tumor onset, mortality-free prevalence and tumor yield. "Historical control data" are considered essential for designing, monitoring, interpreting and evaluating studies of a given type. In addition, a compilation of such control data can illustrate trends or provide measures of reproducibility more reliably than can individual studies. This data set shows how clearly the UVR-induced skin tumor onset time is dependent on UVR dose, how skin tumors develop sooner in female mice than in male mice at a low UVR exposure dose, and that topical administration of certain vehicle formulations can enhance photocarcinogenesis.
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