Quantitative and qualitative changes in dermal collagen and elastin occur in response to chronic ultraviolet (UV) irradiation. These changes have been implicated in the genesis of the wrinkling seen in chronically irradiated, or photoaged skin. We examined the relationship between wrinkle formation and changes in dermal structural protein content and type. Skh-1 hairless mice were irradiated with suberythemal doses of UV-B three times a week for up to 20 wk. Visible wrinkling was present after 6-7 wk of irradiation. Dermal elastic fiber content was quantified by color image analysis of paraffin-embedded tissue. There was no significant difference in dermal elastic fiber content between irradiated and age-matched control mice after either 10 or 20 wk of irradiation. The effect of UV-B irradiation on total dermal collagen content, ratio of collagen type III-type I, and extent of glycosylation and crosslinking of collagen was no different in irradiated and age-matched control mice after 10 wk of irradiation. Increased epidermal thickness was evident in frozen sections after 6 wk of irradiation, and the thickness increased with continued irradiation. Dermal thickening was evident after 10 wk of irradiation. Sufficient UV-B irradiation will eventually cause changes in dermal elastin and collagen content; however, wrinkle formation precedes such changes. A causal relationship between wrinkle formation and dermal structural protein content changes in Skh-1 hairless mice could not be established in this study.

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The ability of different classes of hydrazine derivatives to modify cytochrome P-450 function during turnover as judged by loss of absorbance at 416 nm, loss of CO-reactive cytochrome P-450, or destruction of haem has been studied. Addition of monosubstituted hydrazines to rat-liver microsomes caused considerable loss of CO-reactive cytochrome P-450 and haem destruction; monosubstituted hydrazides caused mainly loss of CO-reactive cytochrome P-450, most likely due to abortive complex formation. Metabolism of 1,1-disubstituted hydrazines by microsomal cytochrome P-450 resulted in loss of CO-reactive cytochrome P-450 only, with no haem destruction. The 1,2-disubstituted hydrazines and hydrazides, procarbazine and iproniazid, acted similarly to the monosubstituted hydrazines, while 1,2-dimethylhydrazine elicited no response, either in observable spectral changes or loss of CO-reactive cytochrome P-450. Synthetic diazene intermediates of phenylhydrazine and N-aminopiperidine reacted rapidly with microsomal cytochrome P-450 to form a spectral intermediate resembling the putative iron porphyrin-diazenyl complex. The decomposition of certain iron porphyrin-diazenyl derivatives apparently leads to destruction of the porphyrin prosthetic group, most likely due to haem alkylation.

There is much controversy regarding the ability of sunscreens to prevent ultraviolet (UV)-induced immune suppression. Epidermal Langerhans cells (LC) play a key antigen-presenting role in the afferent limb of the immune system's response to antigens introduced through the skin. It has been suggested that depletion of LC in UV-exposed skin is a critical step toward the induction of immunosuppression by UV radiation. There are a number of disparate reports with inconsistent results concerning the ability of sunscreens to prevent UV-induced depletion of LC. The purpose of this study was to systematically evaluate the ability of sunscreens to prevent UV-induced LC depletion in mice. Epidermal sheets obtained from skin biopsies taken from mice exposed to UV radiation from Kodacel-filtered FS20 sunlamps, which do not emit UV power at wavelengths < 290 nm, were immunoperoxidase stained for LC using a rat monoclonal antibody against mouse Ia (major histocompatibility complex class II antigen). Time course and dose-response curves for LC depletion were generated for Skh-1 and C3H mice. Dose-response curves for acute UV exposure induced depletion of LC in Skh-1 and C3H mice were similar, but not identical. LC density in the skin of Skh-1 mice that received chronic UV exposure (3 days/week for 8 weeks) was reduced by 62% after 2 weeks of exposure, but returned to normal levels by 6 weeks. Five commercial sunscreen lotions with labeled sun protection factors (SPF) of 4, 8, 15, 30 and 45 were tested for their capacity to block UV-induced depletion of LC. LC were depleted approximately 75% in the skin of unprotected or placebo lotion treated Skh-1 mice exposed to UV given on two consecutive days. Conversely, LC depletion was prevented in similarly UV exposed Skh-1 mice protected with a SPF 30 sunscreen. In C3H mice the levels of protection against LC depletion provided by the five sunscreens were proportional to the level of protection predicted by their labeled SPF. Comparisons of dose-response curves showed that significantly higher doses of UV were required for LC depletion and induction of skin edema than for the induction of local suppression of contact hypersensitivity. Thus, at UV doses where sunscreens provide complete protection against immunosuppression of contact hypersensitivity, prevention of LC depletion and skin edema would be expected.

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