P. D. Forbes

An action spectrum for uv photocarcinogenesis

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.

Enhancement of experimental photocarcinogenesis by topical retinoic acid.

Topical application of retinoic acid (RA) solutions greatly enhanced the response of hairless mouse skin to a moderate dose of simulated sunlight. Tumors appeared much earlier, and in much greater numbers, in animals treated daily with 1 or 10 micrograms of RA in methanol immediately after 2 h exposure to a xenon arc filtered through 2 mm of Schott WG 320 glass (approximately equivalent in human erythema effectiveness to 5 min of mid-summer noon solar exposure in northern mid-latitudes), compared to mice treated with light and methanol only. The higher amount of RA, in combination with light, produced moderate epidermal hyperplasia and some scaling and transient erythema, but no gross ulceration or inflammation of skin. The lower amount of RA, though about equally effective in carcinogenesis, produced minimal epidermal hyperplasia compared to the ultraviolet radiation + methanol control.

Inhibition of Ultraviolet Radiation-Induced Skin Tumors in Hairless Mice by Topical Application of the Sunscreen 2-Ethyl Hexyl-P-Methoxycinnamate

AbstractThis study used simulated solar ultraviolet radiation (UVR) exposure of hairless mice to produce skin tumors and 12-o-tetradecanoyl-phorbol-13-acetate (TPA) to increase the likelihood of tumor expression. We evaluated the protection afforded by several concentrations of a sunscreen ingredient (by measuring reduction of “promotable” effects initiated by UVR); the data show that 2-ethyl hexyl-p-methoxycinnamate (2-EHMC) provided protection against photocarcinogenesis (the level of protection increasing with concentration of sunscreen). A second sample of 2-EHMC (drawn from a different production batch) also suppressed photocarcinogenesis but less effectively than the first sample. The study was also useful for evaluating whether the test agents could act as initiators in the two-stage process of tumorigenesis. The data show that repeated applications of TPA did not promote tumor growth in skin pretreated with any sunscreen ingredients alone (i.e., either sample of 2-EHMC in the absence of UVR).

Effect of Indoor Lighting on Normal Skin

A small but measurable component of some indoor lighting is ultraviolet radiation (UVR); whether it is sufficient to modify the indoor workers risk for chronic skin changes is not directly answerable with available technology. A first approach to this question involves a) estimating a range of annual background solar exposure for indoor workers currently at risk; b) determining whether, and at what levels, UVR exposure is a part of specified indoor lighting; and c) calculating the increment in risk implied by a and b. This algorithm predicts that some lighting conditions that meet NIOSH recommended standards would still result in significant increases in the risk of cumulative UVR damage, including skin cancer. More information concerning actual exposure conditions, the relation of spectral effectiveness for luminosity and UVR production, and dose-time reciprocity are required to improve our predictions of long-term cutaneous effects of indoor lighting.

Effects of chemicals on photobiologic reactions of skin.

Human attitudes toward sunlight are equivocal. Almost everyone experiences psychological, and possibly physical benefits from exposure to the sun. In contrast, most people recognize an imminent danger of overexposure, with painful and, occasionally, serious consequences.

Drug Products and Photocarcinogenesis

Most safety tests are designed to determine whether an agent, such as a drug or chemical, will adversely affect some normal physiological component or process. In contrast, most photobiological safety tests seek to determine whether a chemical can amplify the known noxious effects of an external agent, ultraviolet radiation (UVR). Tests for phototoxicity, for example, determine whether suberythemal doses of radiation will produce acute damage in the presence of the test agent: such tests are always preceded by a determination that the agent alone does not produce such damage. It is understood that higher doses of UVR (or, in some cases, different radiation spectra) are capable of producing erythema in the absence of the test agent, but for testing purposes the effects of low doses of UVR are regarded as the “normal” state against which toxic effects are to be evaluated. Tests for photoallergic properties may go even further in altering the reference “normal” state, by imposing various forms of trauma at either initiation or elicitation stages. The justification for introducing external trauma in a photobiological safety test is the assumption that some exposure to environmental UVR is virtually inevitable; thus an agent which can intensify trauma induced by UVR is capable of intensifying a “normal” and expected biological response.

Experimental Ultraviolet Carcinogenesis

Cancer, it has been said, is an environmental problem. As long as we live on the surface of the earth, we will have to deal with what must be the most ubiquitous carcinogen of all—sunlight. Soon after the recognition that ultraviolet radiation (UVR) could act as a carcinogen, a number of investigators attempted quantitative studies and made efforts to identify mechanisms of photocarcinogenesis. These aims were central to the investigations that Blum(1) and his colleagues performed at the National Institutes of Health during the 1940’s and 1950’s. The thrust of the Blum experiments was an effort to describe the relation of stimulus (UVR) to response (tumor formation and development) in quantitative terms. These data made a unique contribution to the cancer literature, and they remain an important component in the evolution of quantitative models of the carcinogenesis process. It is safe to predict that such models will continue to appear.

Chemical Modifiers of Photocarcinogenesis

It is widely claimed that much cancer is of environmental origin. The term is used to include such varied factors as diet, natural and modified atmospheric constituents, occupational exposure to chemicals, and sources of ionizing radiation. The emphasis on environmental effects is based, in some cases, on a desire to minimize concern for possible hazards of consumer products, or in other cases to focus attention on hazards of the workplace.