DNA ploidy changes in rhino mouse skin induced by all-trans retinoic acid and retinol.
OBJECTIVE
In order to assess the proliferative changes induced by all-trans retinoic acid (RA) and retinol (ROL), we have carried out a study of the DNA content of basal and suprabasal keratinocytes after epicutaneous application on the rhino mouse.


METHODS
Skin sections were analyzed stereologically and cytophotometrically using the Feulgen technique. The diploid DNA value (2C) was obtained from hepatocyte nuclei of control animals. Whereas cells in phase G0-G1 will show a 2C content, cells during phase S and in phase G2-M will show DNA values ranging from 2C to 4C and 4C, respectively.


RESULTS
Although epidermal thickness (ET) increased significantly in all treated animals, surface density only increased in animals treated with all-trans RA. Quantification of DNA content of basal keratinocytes showed reduction of 2C and 2C-4C populations with a commensurate increase in proportions of cells with 4C and > 4C in the animals treated with 0.025% all-trans RA and ROL. Suprabasal keratinocytes of mice treated with 0.025% all-trans showed a decrease of the 2C population and an increased proportion of cells with 4C. Whereas 0.025% all-trans RA induced an increase of both basal and suprabasal DNA indices, ROL enhanced only the basal DNA index significantly.


CONCLUSIONS
Animals treated with 0.025% ROL showed a significant increase in the basal proliferative index (PI) while the suprabasal PI remained constant; treatment with 0.025% all-trans RA produced a significant increase of both basal and suprabasal PIs and parakeratotic hyperkeratosis probably due to incomplete differentiation.
González
S
S
Wellman Laboratories of Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, USA. gonzalsa@helix.mgh.harvard.edu
Alcaraz
M V
MV
Díaz
F
F
Flotte
T J
TJ
Pérez de Vargas
I
I
Anderson
R R
RR
Kollias
N
N
D000279:Administration, Cutaneous; D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis*; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006965:Hyperplasia; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007641:Keratolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008812:Mice, Hairless; D008817:Mice, Mutant Strains; D011003:Ploidies; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology*; D014801:Vitamin A / Q000008:administration & dosage / Q000494:pharmacology*
D007641:Keratolytic Agents; D014801:Vitamin A; D014212:Tretinoin; D004247:DNA