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Biomedical subjects

P D Forbes

Publications and source records attributed to P D Forbes.

At least 19 recordsLinked to original sources
PubMed1991

Tumors of the skin in the HRA/Skh mouse after treatment with 8-methoxypsoralen and UVA radiation.

8-Methoxypsoralen (8-MOP) with and without UVA radiation was administered to HRA/Skh mice (36 animals per treatment group) three times a week in the feed for a total dose of 9-80 mg/kg/week for 52 weeks. Most of the animals at the top dose of 8-MOP with UVA radiation had developed skin toxicity and/or skin tumors by 52 weeks. The skin lesions seen after treatment with 8-MOP and UVA radiation were characterized as squamous cell hyperplasia, squamous cell papilloma, and squamous cell carcinoma and are similar to what has been reported in humans after exposure to 8-MOP and UVA. Squamous cell hyperplasia and acute inflammation of the cornea were also seen in some of the treated female mice. Oral administration of 8-MOP and UVA did not result in a carcinogenic response to other organ systems. There were no increases in skin neoplasms after 8-MOP or UVA radiation alone. 8-MOP given in combination with UVA was carcinogenic to the skin of mice at dose levels similar to those used to treat psoriasis in humans.

Animals↗
PubMed1989

Sunscreen testing using the mouse ear model.

During the developmental stages of sunscreen formulation it is desirable to have a simple, accurate and inexpensive biological model to test product effectiveness. Another desirable attribute is a quantitative, unbiased response endpoint for evaluation. We have developed such a test system based upon the ear swelling response of hairless albino mice. With this system, irradiation times are greatly reduced; furthermore, the response parameter is metric and can be determined noninvasively with an inexpensive micrometer. Protection factors determined with the mouse ear model show high correlation with the sun protection factors as determined on human subjects (r = 0.92) and were linearly related over a wide range of values. This new method affords a simple, accurate and inexpensive system for evaluation of efficacy and safety of new products.

Animals↗
PubMed1987

Toxicity of 8-methoxypsoralen, 5-methoxypsoralen, 3-carbethoxypsoralen, or 5-methylisopsoralen with ultraviolet radiation in the hairless (HRA/Skh) mouse.

An experimental design to simulate PUVA therapy (oral 8-methoxypsoralen followed by uv radiation) has been tested in a 13-week subchronic study to determine the relative toxicities of 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), 5-methylisopsoralen (5-MIP), and 3-carbethoxypsoralen (3-CEP) in inbred hairless mice (HRA/Skh). Drug was administered by 1-hr pulse feedings three times a week after mice were fasted overnight; individually housed animals were then exposed to uv radiation (320-400 nm; less than 2% output less than 320 nm). 8-MOP or 5-MOP administered orally (at doses of approximately 240 or 480 mg/m2 body surface area per week) followed one-half hour later with uv radiation of 2 J/cm2 for 13 weeks were found to cause skin toxicity including inflammation, hyperplasia, ulceration, and cellular atypia. Dose-related toxicity was not seen in other organ systems. Corresponding levels of 5-MIP or 3-CEP with uv radiation did not produce skin toxicity. These studies show that the psoralens with two potential DNA-binding sites (8-MOP and 5-MOP) were more toxic than psoralens with only one photoreactive site (5-MIP and 3-CEP).

5-Methoxypsoralen↗
PubMed1986

Ocular effects of treatment with various psoralen derivatives and ultraviolet-A (UVA) radiation in HRA/Skh hairless mice.

Hairless (HRA/Skh) mice were administered one of four dietary concentrations (50, 100, 625 or 1250 ppm) of 8-methoxypsoralen (8-MOP) or 5-methoxypsoralen (5-MOP), or molar equivalent concentrations of 5-methylisopsoralen (5-MIP) or 3-carbethoxypsoralen (3-CPS) by 'pulse feeding' technique, 3 days per week for 13 weeks. For the final 11 weeks psoralen derivative administration was followed by exposure to 0.2 or 48 J/cm2 of unfiltered ultraviolet-A (UVA) radiant energy from FR74T12PUVA lamps. At 0 and 13 weeks eyes were dilated with 0.2% atropine solution and were examined using a binocular indirect ophthalmoscope with a +20.0 D condensing lens. The lids, cornea, anterior chamber and the lens were evaluated for pathological changes. Ocular damage consisting of dense central corneal opacification was seen at significant levels in animals given 8-MOP or 5-MOP and exposed to UVA. In addition, opacities in the area of the posterior lens were seen in all experimental groups and appeared to be related to drug treatment, independent of light exposure, and therefore appeared not to be related to drug-light interaction. Some corneal and lenticular opacification was seen at non-significant levels in all experimental and control groups.

5-Methoxypsoralen↗
PubMed1985

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 worker's 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.

Erythema↗
PubMed1979

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.

Administration, Topical↗
PubMed1979

Aging, environmental influences, and photocarcinogenesis.

Repeated exposure of human skin to solar ultraviolet radiation (UVR) over a period of many years is responsible for the induction of most nonmelanoma skin cancers in man. The tumors are progressively more common in chronologically older people. Is this fact purely a function of adequate dose accumulation and development time, or is tumor expression influenced by "physiological age"? The answer to this question influences risk estimates of the results of atmosphere modification. Data from animal studies indicate that the tumor incidence is affected by dose-delivery factors and not just by the accumulated lifetime dose. In addition, young mice are more prone to tumor induction by a given UVR dose than are older animals. Because the quanlity and quantity of the stimulus (UVR) can be readily manipulated and accurately described, studies on photocarcinogenesis offer distinct possibilities for untangling some of the interactive variables in the aging process.

Aged↗
PubMed1978

Experimental ultraviolet photocarcinogenesis: wavelength interactions and time-dose relationships.

Tumors were induced in the skin of SKH hairless mice by exposure to fluorescent FS sun lamps or to a long-arc xenon solar simulator. Tumores developed about equally well with varying amounts of UV-A radiation (lambda greater than 320 nm) given simultaneously. In contrast, incremental changes in the UV-B region (lambda less than 320 nm) led to substantial increases in carcinogenic effectiveness. A tumor-"initiating" dose of UV-B (4-10 wk of daily FS lamp exposures) was rendered less effective by subsequent exposures of the mice to UV-A (6 hr/day, F-40 T12BL lamps). The mechanism for this effect is not known. Most tumors induced by a short course (10 wk) of FS lamp exposure grew slowly or regressed, whereas mice exposed for a longer period (30 wk) developed more tumors, and many of those that appeared early grew aggressively. Effects of daily dose fractionation were less clear, and the subject requires further study. These and other variables are being tested in a program designed to yield useful information on the effects of changing spectrum, dose, and dose delivery rates on sunlight-induced cancer.

Animals↗
PubMed1977

Diester waxes from skin lipids of the feet of biotin depleted and biotin supplemented turkey poults.

The neutral lipids of the skin from the feet of turkey poults fed a biotin supplemented or a biotin deficient diet consist mainly of triacyglycerols, and of mono- and diester waxes. Diester waxes from both groups were characterized as fatty acid esters of erythro-2,3-alkanediols. A comparison between fatty acid composition of the two groups, however, revealed the following significant differences. Biotin deficient birds showed a fairly high concentration of very long chain fatty acids (C36-C40) which were completely absent in biotin supplemented birds. Further, almost one-third of the fatty acids of diester waxes in biotin deficient birds were unsaturated while those from biotin supplemented birds were predominantly (96%) saturated.

Animals↗
PubMed1976

Modification of photocarcinogenesis by two immunosuppressive agents.

The carcinogenic effect of ultraviolet radiation (UVR) on the skin of hairless (hr) mice was modified by two immunosuppressive agents, rabbit anti-mouse lymphocytic serum (ALS), and 6-mercaptopurine (6MP). Daily exposure of mice to UVR resulted in multiple tumor production. Carcinogenesis was measured in terms of affected mice (prevalence) and numbers of tumors produced. By both criteria, photocarcinogenesis was enhanced by ALS but inhibited by 6MP.

Animals↗