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DNA ploidy changes in rhino mouse skin induced by all-trans retinoic acid and retinol
S González1, M V Alcaraz, F Díaz
1Wellman Laboratories of Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, USA. gonzalsa@helix.mgh.harvard.edu
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.
Study Design:
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.
Conclusion:
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.