Linoleic acid effects on epidermal DNA synthesis and cutaneous prostaglandin levels in essential fatty acid deficiency.

An essential fatty acid (EFA) deficient state has been induced in hairless mice. The epidermal changes included hyperkeratosis, hypergranulosis and acanthosis. Epidermal DNA synthesis was increased 3-fold compared with normal diet mice. Prostaglandin E (PGE) and prostaglandin F (PGF) levels, measured by radioimmunoassay, were much reduced in the EFA deficient mice skin. 10% Linoleic acid applied topically for 2 weeks corrected the gross and histological skin abnormalities and reduced epidermal DNA synthesis to normal values. The levels of PGE and PGF were only partially corrected. Linoleic acid applied to normal diet mice increased skin levels of PGE and PGF compared with the control vehicle treated normal diet mice. These results provide further evidence for the importance of essential fatty acids in the control of epidermal proliferation and differentiation. The importance of PGE and PGF in controlling epidermal DNA synthesis in EFA deficiency is less clear.

The hairless mouse as a model for evaluating sunscreens. Prevention of ultraviolet B inhibition of epidermal DNA synthesis.

A sunscreen's effectiveness is usually determined by its ability to prevent ultraviolet (UV) radiation-induced skin erythema. This criterion requires subjective interpretation. We propose a new method of evaluating sunscreens based on the known effect of UV-B radiation (290 to 320 nm) to inhibit DNA synthesis. Using hairless mice, we found that sulisobenzone (Uval) and aminobenzoic acid (PreSun) sunscreens differ substantially in their ability to prevent inhibition of epidermal cell DNA synthesis by UV-B radiation. By estimating the UV-B dose required to inhibit DNA synthesis by 50%, with and without sunscreen, a protective factor of 5.6 and 14.4 was calculated for sulisobenzone and aminobenzoic acid, respectively. This technique is an objective way to evaluate sunscreen effectiveness and could be a useful screening procedure for sunscreen preparations before final efficacy testing in humans.

Anthracene with near ultraviolet light inhibiting epidermal proliferation.

Anthracene plus near ultraviolet (UV) light (UV-A, 320 to 400 nm) suppresses DNA synthesis and mitosis in mouse epidermis. Ultraviolet-A light or anthracene alone does not have any effect. There is no photoactivation of anthracene to enhance depression of DNA synthesis by either UV-B (290 to 320 nm) or UV-C (254 nm) light. While methoxsalen with UV-A light inhibits DNA synthesis, the phototoxic drugs chlorpromazine hydrochloride and demethylchlortetracycline do not. The combination of anthracene plus UV-A light may have therapeutic effectiveness for psoriasis with less potential for photocarcinogenesis than psoralens plus UV-A light.

Topical spermine and putrescine stimulated DNA synthesis in the hairless mouse epidermis.

Polyamines were applied topically to the skin of the hairless mouse. Putrescine stimulated the incorporation of thymidine after a 24-h application period. The effect of polyamines upon skin pretreated with a potent topical steroid was also examined; in this model thymidine incorporation was stimulated by both spermine and putrescine. Pretreatment was performed in order to reduce endogenous polyamine biosynthesis and increase the sensitivity of the epidermis to exogenous polyamines. Depletion of the activity of ornithine decarboxylase, the rate-limiting polyamine biosynthetic enzyme, by topical steroids was confirmed in the hairless mouse following induction of the enzyme by UV-B. The results are consistent with those in vitro studies suggesting a role for polyamines in the control of DNA synthesis; the effect of corticosteroids upon proliferative skin disorders may be mediated through this mechanism.

Suppression of epidermal proliferation by ultraviolet light, coal tar and anthralin.

360 nm ultraviolet light (UVA) plus coal tar depresses mitosis and DNA synthesis in epidermal cells. UVA has no effect by itself. In some models coal tar alone can partially depress DNA synthesis. 254 nm ultraviolet light (UVC) and 290--320 nm ultraviolet light (UVB) do not enhance depression of DNA synthesis by coal tar. Dithranol will suppress mitosis and DNA synthesis of epidermal cells but there appears to be no photo-activation by UVA. Dithranol suppression and suppression of DNA synthesis by UVB or UVC are additive when used together.