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The dynamics of human pigmentation in response to ultraviolet radiation (UVR) remain poorly characterized. In part, this is attributable to methodological issues relating to the overlap in spectra of hemoglobin and melanin. We describe a new method, based on the recording of reflectance properties following iontophoresis of a potent vasoconstrictor, noradrenaline. This removes the influence of blood, allowing measurement of pigmentation, represented as L* on the L*a*b* scale. Blood flow was separately assessed using laser Doppler flowmetry. We show that there is a clear dose response with the dose of UVR administered, that pigmentation peaks at 1 wk and declines over the following 10 wk, but does not return to baseline within this period. We show clear differences in the degree, but not the temporal pattern of pigmentation between different pigmentary groups. We also report that the relation between facultative pigment and constitutive pigment is incomplete, with a wide scatter of responses for the development of pigmentation irrespective of constitutive levels. For comparison we also document overall photoadaptation and relate changes in pigmentation to the overall changes in photoadaptation.

We have studied the cutaneous response to ultraviolet radiation, measured objectively as erythema in a sample of 12 body sites on 15 Northern European subjects with multiple doses of ultraviolet B (UVB). Skin pigmentation and the development of photoadaptation in response to five repeated doses of irradiation at three body sites was also measured. We report striking differences of up to 5-fold at different body sites to the same challenge dose (p < 0.001) and demonstrate that for this population, site variation is just as important as between-person variation. Skin color at each body site is a strong predictor of response (p < 0.001) and that this cannot be attributed to vascular differences, but instead we believe it reflects site-specific variations in melanin pigmentation. We also observed similar but smaller within-person effects for responses to another inflammatory agent, dithranol (p < 0.01). Despite this, we did not find evidence for differences in the development of photoadaptation by body site. These results have clear clinical implications for the practice of phototesting prior to commencing phototherapy, for therapeutic failure in sites such as the legs in patients with psoriasis, and perhaps for melanoma body-site distribution.

The relationship between skin colour and experimental exposure to ultraviolet radiation (UVR) B, with response measured as erythema was studied. Two reflectance methods were used to measure skin colour--tristimulus colorimetry using a Minolta instrument (summarized as the alpha characteristic angle) and the melanin index based on the Diastron reflectance instrument. As expected both measures are highly correlated (0.91). A dose-dependent relationship between skin colour measured as the alpha characteristic angle and UVR was established, with the gradient increasing from 0.99 at 119 mJ to 2.7 at 300 mJ, with the relevant standard errors being 0.39 and 0.47, respectively. Similarly, for the melanin index (where the scale goes in the opposite direction) the gradient differs between -0.49 for 119 mJ and -0.91 for 300 mJ, with the standard errors being 0.14 and 0.17 respectively. The proportion of variation explained is also greater at higher UVR challenge doses. Studies relating UVR sensitivity and pigmentation need to take account of the dose of UVR administered.

It has previously been reported that the time course of erythema may be delayed in those with sun-sensitive skin types and those with skin cancer. One molecular explanation for this putative phenotype would be that it is caused by mutations of the melanocortin 1 receptor (MC1R). In the present study of 20 persons, 10 of whom were MC1R homozygous, we measured erythema over a 21-day period in response to a range of ultraviolet B doses using methods that improved on previous studies. We could detect no consistent differences in ultraviolet radiation-induced erythema between the groups studied. The pharmacological mechanisms underpinning such prolonged inflammatory responses merit further investigation.

Please cite this paper as: The physiological and phenotypic determinants of human tanning measured as change in skin colour following a single dose of ultraviolet B radiation. Experimental Dermatology 2010; 19: 667-673. Abstract: Experimental study of the in vivo kinetics of tanning in human skin has been limited by the difficulties in measuring changes in melanin pigmentation independent of the ultraviolet-induced changes in erythema. The present study attempted to experimentally circumvent this issue. We have studied erythemal and tanning responses following a single exposure to a range of doses of ultraviolet B irradiation on the buttock and the lower back in 98 subjects. Erythema was assessed using reflectance techniques at 24 h and tanning measured as the L* spectrophotometric score at 7 days following noradrenaline iontophoresis. We show that dose ( P < 0.0001), body site ( P < 0.0001), skin colour ( P < 0.0001), ancestry ( P = 0.0074), phototype ( P = 0.0019) and sex ( P = 0.04) are all independent predictors of erythema. Quantitative estimates of the effects of these variables are reported, but the effects of ancestry and phototype do not appear solely explainable in terms of L* score. Dose ( P < 0.0001), body site ( P < 0.0001) and skin colour ( P = 0.0365) or, as an alternative to skin colour, skin type ( P = 0.0193) predict tanning, with those with lighter skin tanning slightly more to a defined UVB dose. If erythema is factored into the regression, then only dose and body site remain significant predictors of tanning: therefore neither phototype nor pigmentary factors, such as baseline skin colour, or eye or hair colour, predict change in skin colour to a unit erythemal response. [ABSTRACT FROM AUTHOR]

This article reports that previous studies have shown variation in erythemal responses between some different body sites. But, no previous study has systematically attempted to partition and contrast variation within persons with that between persons using appropriate statistical and experimental methodology. Prior to the advent of appropriate quantification of erythemal reactions by researchers in the 1980s, assessments relied on visual inspection of erythema, a method that is inadequate for the task at hand.

The mechanisms mediating the varied effects of ultraviolet radiation (UVR) on human skin are unclear, although a relationship between erythema and DNA damage is suggested by photosensitivity in xeroderma pigmentosum. Increased p53 expression in response to UVR is thought to reflect direct DNA damage, but recent evidence indicates that UVR also activates membrane and cytosolic signal transduction pathways. In this study, we have investigated the relationship between erythema and p53 induction following UVB and whether this p53 response is specific to UVR. p53 protein expression was determined by immunocytochemistry using the monoclonal antibody DO7, and p53 mRNA expression was examined by non-isotopic in situ hybridization. Incremental doses of UVB were administered to the lower back of eight subjects. Immunostaining revealed that p53 positive nuclei were significantly increased 8 h after suberythemogenic doses of UVB (79 ± 12), compared to normal unirradiated skin (8 ± 6, p < 0.0005), but no change in p53 mRNA was seen. Higher UVB doses, which resulted in moderate erythema, resulted in a similar or greater induction of p53 protein. Indomethacin (1% w/v), applied immediately after UVB irradiation, significantly inhibited UVB erythema at 8 h in six subjects (p < 0.005), but did not reduce p53 immunostaining. Dithranol (1 μg/μl, n = 8), sodium dodecylsulphate (5%, n = 4), and retinoic acid (0.5%, n = 4), applied for 48 h, caused erythema, significantly increased p53 protein levels (p < 0.05), and also increased p53 mRNA. Our results show that in human skin, UVB-induced p53 elevation can be dissociated from erythema and skin irritants can also induce p53 protein. The induction of p53 mRNA by irritants but not UVR suggests different mechanisms of action. [ABSTRACT FROM AUTHOR]