Lifetime topical application of tretinoin to hairless mice.
The discovery that topical tretinoin can reverse some of the effects of photodamage may lead to its chronic application. Examination of long-term effects was of interest. Three groups of hairless mice (age 6-8 weeks) were treated dorsally with 1) tretinoin (0.025%), 2) cream vehicle, 3) sham treatment. Applications were 3 times weekly and continued for up to 2 years until all mice were sacrificed or had died. Biweekly examinations showed no sign of retinoid toxicity, with growth and longevity similar in all groups. Tretinoin-treated skin was smooth and pink, resembling that of younger mice. Controls had yellowed, irregularly thickened skin. Histologically, tretinoin-treated skin had a hyperplastic epidermis consisting of plump, cytologically normal cells. Control skin had 3-4 compressed cell layers. Foci of new normally staining collagen were present in the subepidermal dermis of tretinoin-treated skin; fibroblasts were large and abundant in these areas. These foci were absent in controls. Mice treated with tretinoin also appeared to have increased amounts of elastic fibers and glycosaminoglycans.
Kligman
L H
LH
Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia 19104.
Mezick
J A
JA
Capetola
R J
RJ
Thorne
E G
EG
D000279:Administration, Cutaneous; D000818:Animals; D001485:Basement Membrane / Q000187:drug effects; D003094:Collagen / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004547:Elastic Tissue / Q000187:drug effects; D004817:Epidermis / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006965:Hyperplasia / Q000139:chemically induced; D051379:Mice; D008812:Mice, Hairless; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology* / Q000633:toxicity
D014212:Tretinoin; D003094:Collagen