CHRONIC UVB-INDUCED AND ALL-TRANS RETINOIC-ACID-INDUCED QUALITATIVE AND QUANTITATIVE CHANGES IN HAIRLESS MOUSE SKIN

Histochemical and ultrastructural studies have already demonstrated th at chronic exposure to UV radiation induces profound alterations in al l structural elements of the skin and that topical all-trans retinoic acid (tRA) can substantially correct much of the tissue damage. Howeve r, previous biochemical studies on dermal components of the extracellu lar matrix have led to contradictory results, particularly with regard to the effect of chronic UV exposure. The aim of our study was to inv estigate changes in collagen content and other dermal modifications in duced by tRA in irradiated and non-irradiated hairless mouse skin. Hai rless mice were exposed to increasing doses of UVB for 10 weeks (the c umulative total dose was 4.6 J cm(-2)). After the UV irradiation perio d the animals were treated with 0.05% tRA or with ethanol-polyethylene glycol vehicle alone three times a week for up to 10 weeks. Non-irrad iated animals underwent the same treatments. The main clinical and his tological changes induced by UVB exposure were erythema, wrinkling, ke ratosis and epidermal thickening. Following UVB exposure, tRA treatmen t did not improve the clinical aspect but increased the width of the d ermal repair zone. Fibronectin, laminin and type I and VI collagens we re detected by indirect immunofluorescence techniques in this zone. Ty pe I and III collagens were quantitated in skin fragments after cyanog en bromide digestion and polyacrylamide gel electrophoresis. Under our experimental conditions, UVB irradiation alone induced neither change s in total collagen nor in type I and III collagen levels. tRA treatme nt of irradiated skin significantly increased both type I and III coll agen levels by factors of 1.33 and 1.88 respectively. The ratio of typ e III to types I+III increased significantly. Topical tRA also increas ed collagen type levels in non-irradiated hairless mouse skin. Type I collagen increased proportionally to type III. This study leads to the conclusion that topical tRA exerts direct or indirect effects on coll agen metabolism in irradiated as well as non-irradiated hairless mouse skin.