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Biomedical subjects

Frederick Urbach

Publications and source records attributed to Frederick Urbach.

3 recordsLinked to original sources

Standardized protocols for photocarcinogenesis safety testing.

Solar ultraviolet radiation (UVR) is recognized as a major cause of non-melanoma skin cancer in man. Skin cancer occurs most frequently in the most heavily exposed areas and correlates with degree of outdoor exposure. The incidence of skin cancer is also increased by contact with photosensitizing drugs and chemicals such as psoralens, coal tars and petroleum stocks. Other substances which do not act as photosensitizers, such as immunosuppressants taken by organ transplant recipients, also increase the risk of skin cancer. The U.S. Food and Drug Administration requests, on a case-by-case basis, that risk of enhanced photocarcinogenesis is assessed for many classes of drugs. Health Canada's Therapeutic Products Programme has issued a Notice of Intent to regulate pharmaceutical products which may enhance carcinogenicity of the skin induced by ultraviolet radiation. Other national regulatory agencies review such data when they exist, but their own requirements emphasize batteries of short-term in vitro and in vivo tests. While they may support drug development strategies, short-term tests have yet to be validated as predictors of the ability of drugs or chemicals to enhance photocarcinogenesis. Published protocols now describe study designs and procedures capable of determining whether test agents enhance the rate of formation of UVR-induced skin tumors.

Animals↗

UV doses of young adults.

Since 1986, people have been informed that they get about 80% of their lifetime ultraviolet (UV) dose by the age of 18. This belief originated from the mathematical conclusion that diligent use of sunscreens (sun protection factor 15 or higher) during the first 18 years of life would reduce the lifetime incidence of nonmelanoma skin cancers by 78%. These data were misconstrued to mean that individuals also got about 80% of their lifetime dose of UV by the age of 18 (linear relationship). However, these calculations were based on the incidence of nonmelanoma skin cancers being related to the square of the UV dose. Careful analysis of UV exposure data shows that Americans actually get less than 25% of their lifetime UV dose by the age of 18. This finding also appears to be true worldwide because Australia, UK and The Netherlands report a similar UV exposure pattern. UV-initiated damage early in life can be promoted by subsequent exposures to progress into tumors later in life. For example, the nonmelanoma skin cancer, squamous cell carcinoma, is dependent on the cumulative UV dose. Thus, a better educational approach for reducing skin cancers would be to instruct fair-skinned individuals to protect themselves throughout their lives from being exposed to too much UV radiation.

Adolescent↗

The historical aspects of photocarcinogenesis.

The concept of photocarcinogenesis is of fairly recent duration. Although cancer of the breast is described in the ancient Greek medical literature, skin cancer is not mentioned even as late as the 18th Century. This is most likely due to the poor survival of humans, 80% of people did not live past 40 years, and only 6% lived longer than 60 years. The first association of skin cancer (face and lip) with outdoor exposure dates to the middle of the 19th Century. About that time it was shown that it was Ultraviolet Radiation (UVR) that could cause skin and eye inflammation. It was not until the 20th Century that competent epidemiologic studies associated human skin cancer with chronic solar exposure, and it was shown that chemicals could augment the effects of UVR exposure. It has only been in the last quarter of a Century that it was found that UVR could cause immunologic changes that allow multiple skin cancers to develop. Advances in molecular biology have begun to show the cellular and molecular events that lead to UVR induced skin carcinogenesis.

Animals↗