A comparative study of the induction of epidermal hyperplasia by natural and synthetic retinoids.

Retinoids are potent inducers of epidermal hyperplasia. In the present study the ability to induce epidermal hyperplasia by a variety of retinoids has been compared. Thirteen retinoids and beta-carotene were applied topically in an acetone vehicle to the dorsal skin of hairless mice and the dose-response and time course for the induction of hyperplasia were measured. Peak hyperplasia occurred 4 to 5 days after a single topical dose, and was induced by doses well below those producing gross or histological signs of cutaneous toxicity. The induction of hyperplasia was dose-dependent, the number of epidermal cell layers increasing initially in proportion to the log of the dose and then tending to plateau or, in some cases decrease, after which further increases in dose were associated with the appearance of gross and histological toxicity. The slopes of the initial increasing phase were determined and potencies expressed as the dose producing a 50% increase in the number of epidermal cell layers. All-trans-retinoic acid and its analogs, etretinate and its free acid, (E)-4[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl- 2-naphthalenyl)-1-propenyl]-benzoic acid (arotinoid) derivatives, retinol and retinal produced an increase in the number of cell layers proportionate to the log of the dose. Decarboxylated (E)-4[2-(5,6,7,8-tetrahydro-5,5,8,8- -tetramethyl-2-naphthalenyl-1-propenyl]-benzoic acid, a cis-locked aryl triene derivative of retinoic acid and beta-carotene were inactive. Similar time courses were observed when retinoids were dosed p.o. The relative potencies of the retinoids in this system show similar trends to those reported for biological activities measured in other in vivo and in vitro assays.

• Publication year

  1986

• Venue

  Journal of Pharmacology and Experimental Therapeutics

• Publication date

  1986-04-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/s0022-3565(25)25076-5PMID 3958970
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Response of epidermal polyamines to orally administered aromatic retinoid RO 10-9359

  2004cited by this paper
• Pharmacokinetics of topically applied radiolabeled retinoids in hairless mouse epidermis and dermis after single applications.

  1985cited by this paper
• Histologic changes in the skin of the rhino mouse (hrrhhrrh) induced by retinoids.

  1984cited by this paper
• Induction of ornithine decarboxylase activity and DNA synthesis in hairless mouse epidermis by retinoids.

  1983cited by this paper
• Vitamin A in human skin: I. detection and identification of retinoids in normal epidermis.

  1982cited by this paper
• Retinoic acid induces transglutaminase activity but inhibits cornification of cultured epidermal cells.

  1982cited by this paper
• Response of epidermal cell proliferation to orally administered aromatic retinoid.

  1981cited by this paper
• Aromatic retinoic acid analogues. Synthesis and pharmacological activity.

  1981cited by this paper
• Enzymatic oxidation and reduction of retinal by mouse epidermis.

  1980cited by this paper
• Vitamin A acid effects on epidermal mitotic activity, thickness and cellularity in the hairless mouse.

  1972cited by this paper
• [Stimulation of epidermal DNA syntgesis through vitamin A acid].

  1968cited by this paper
• VISUALIZATION OF THE CELL LAYERS OF THE STRATUM CORNEUM.

  1964cited by this paper
• The effect of vitamin A on epithelial mitosis in vitro and in vivo.

  1961cited by this paper
• On the specificity of the response of mouse epidermis to vitamin A.

  1958cited by this paper

• The Use of Retinoids for the Prevention and Treatment of Skin Cancers: An Updated Review

  2022cites this paper
• Effects of Administration of Vitamin a to Pregnant Dams on the Skin of the Fetuses of Albino Mice

  2014cites this paper
• Topical tazarotene for the treatment of ectropion in ichthyosis.

  2013cites this paper
• Treatment of facial photodamage using a novel retinol formulation.

  2013cites this paper
• Minimally Invasive Treatments and Procedures for Ageing Skin

  2010cites this paper
• Annual Review of Cosmetic Ingredient Safety Assessments: 2005/20061

  2008cites this paper
• Annual Review of Cosmetic Ingredient Safety Assessments—2002/20031

  2005cites this paper
• Evaluation of topical retinoids for cutaneous pharmacological activity in Yucatan microswine

  2004cites this paper
• [Genetic dissection of retinoic acid function in epidermis physiology].

  2002cites this paper
• Therapeutic applications for ligands of retinoid receptors.

  2000cites this paper
• Heterocyclic derivatives of all-trans retinoic acid: in vitro effects on fibroblast/keratinocyte growth and differentiation, and in vivo effects on guinea-pig skin.

  1999cites this paper
• New Concepts for Delivery of Topical Retinoid Activity to Human Skin

  1999cites this paper
• Topical all-trans retinoic acid augments ultraviolet radiation-induced increases in activated melanocyte numbers in mice.

  1999cites this paper
• Receptor specificity of retinoid-induced epidermal hyperplasia: effect of RXR-selective agonists and correlation with topical irritation.

  1997cites this paper
• Suprabasal expression of a dominant-negative RXR alpha mutant in transgenic mouse epidermis impairs regulation of gene transcription and basal keratinocyte proliferation by RAR-selective retinoids.

  1997cites this paper
• An Ultrastructural Study of the Retention Hyperkeratosis of Experimentally Induced Comedones in Rabbits: The Effects of Three Comedolytics

  1996cites this paper
• Chemoprevention of colorectal cancer.

  1996cites this paper
• Negative regulation of two hyperproliferative keratinocyte differentiation markers by a retinoic acid receptor-specific retinoid: insight into the mechanism of retinoid action in psoriasis.

  1996cites this paper
• Dietary vitamin A enhances sensitivity of the local lymph node assay.

  1995cites this paper
• Section Review: Retinoids: Biological Function and Use in the Treatment of Dermatological Diseases: Pulmonary-Allergy, Dermatological, Gastrointestinal & Arthritis

  1995cites this paper
• Topical application of retinoic acid induces murine epidermal proliferation without reducing the cell cycle time. A bivariate BrdUrd/DNA flow cytometric study.

  1995cites this paper
• Effects of etretinate on keratinocyte proliferation and secretion of interleukin-1 alpha (IL-1 alpha) and IL-8.

  1994cites this paper
• Differential effects of topical retinoic acid application on keratin K1 and filaggrin expression in mouse epidermis.

  1994cites this paper
• Effects of Etretinate on Keratinocyte Proliferation and Secretion of Interleukin‐1α (IL‐1α) and IL‐8

  1994cites this paper
• Characterization of Esterase and Alcohol Dehydrogenase Activity in Skin. Metabolism of Retinyl Palmitate to Retinol (Vitamin A) During Percutaneous Absorption

  1994cites this paper
• An in vivo experimental model for effects of topical retinoic acid in human skin

  1993cites this paper
• Effects of all-trans retinoic acid on glycosaminoglycan synthesis in photodamaged hairless mouse skin.

  1993cites this paper
• Retinoid-induced beta-adrenergic inhibitory effect associated with increased thymidine incorporation of fetal rat keratinizing epidermal cells (FRSK cells).

  1993cites this paper
• Retinoic acid metabolites exhibit biological activity in human keratinocytes, mouse melanoma cells and hairless mouse skin in vivo.

  1993cites this paper
• Modification of BHA forestomach carcinogenesis in rats: inhibition by diethylmaleate or indomethacin and enhancement by a retinoid.

  1993cites this paper
• Dry and photo–aged skin:and manifestations management

  1993cites this paper
• Pharmacological effects of retinoids on skin cells.

  1993cites this paper
• Dry and photo-aged skin: manifestations and management.

  1993cites this paper
• Acute or chronic topical retinoic acid treatment of human skin in vivo alters the expression of epidermal transglutaminase, loricrin, involucrin, filaggrin, and keratins 6 and 13 but not keratins 1, 10, and 14.

  1992cites this paper
• Retinoic acid provokes a regeneration-like proliferative response in murine epidermis

  1992cites this paper
• A subpopulation of 12-O-tetradecanoylphorbol-13-acetate-induced papillomas is not inhibited by retinoic acid.

  1992cites this paper
• The Pharmacology of a Novel Topical Retinoid, BMY 30123: Comparison with Tretinoin

  1992cites this paper
• Retinoic acid receptors as regulators of human epidermal keratinocyte differentiation.

  1992cites this paper
• A direct comparison of pharmacologic effects of retinoids on skin cells in vitro and in vivo.

  1991cites this paper
• The noninvasive mouse ear swelling assay. I. Refinements for detecting weak contact sensitizers.

  1991cites this paper
• Morphological differences elicited by two weak acids, retinoic and valproic, in rat embryos grown in vitro.

  1991cites this paper
• Modulation of tumor promotion in mouse skin by the food additive citral (3,7-dimethyl-2,6-octadienal).

  1991cites this paper
• Sequence of morphological events during topical application of retinoic acid on the rhino mouse skin

  1991cites this paper
• BMY 30047: a novel topically active retinoid with low local and systemic toxicity.

  1990cites this paper
• Changes in photo-aged human skin following topical application of all-trans retinoic acid.

  1990cites this paper
• Effects of retinoids on DNA synthesis of pig epidermis: its relation to epidermal beta-adrenergic adenylate cyclase response and to epidermal superoxide dismutase activity.

  1990cites this paper
• Structure-activity relationships of retinoids in developmental toxicology. IV. Planar Cisoid conformational restriction.

  1990cites this paper
• Trans retinoic acid enhances the growth response of epidermal keratinocytes to epidermal growth factor and transforming growth factor beta.

  1990cites this paper
• Percutaneous retinoid absorption and embryotoxicity.

  1990cites this paper
• Retinoic acid induces transforming growth factor-beta 2 in cultured keratinocytes and mouse epidermis.

  1989cites this paper
• Ligand‐specific and non‐specific in vivo modulation of human epidermal cellular retinoic acid binding protein (CRABP)

  1989cites this paper
• Retinoids: Toxicity and teratogenicity to date

  1989cites this paper
• Inclusion of retinoic acid in β-cyclodextrin

  1989cites this paper
• Effects of retinoids on phorbol ester-stimulated epidermal DNA synthesis and hyperplasia in hairless mice.

  1989cites this paper
• The hamster flank organ model: is it relevant to man?

  1989cites this paper
• Retinoids: toxicology and teratogenicity to date.

  1989cites this paper
• Retinoids and Keratinization

  1988cites this paper
• Co‐carcinogenic Effect of Retinyl Acetate on Forestomach Carcinogenesis of Male F344 Rats Induced with Butylated Hydroxyanisole

  1988cites this paper
• Differential effects of retinoids on DNA synthesis in calcium-regulated murine epidermal keratinocyte cultures.

  1988cites this paper
• Oxidation of retinol to retinoic acid as a requirement for biological activity in mouse epidermis.

  1988cites this paper
• Méthodes pour le traitement de lésions solaires de la peau à l'aide de rétinoides

  1987cites this paper
• Verfahren zur Behandlung von Sonnenschädigungen der Haut mit Retinoiden

  1987cites this paper
• The formation of all-trans-retinoic acid from all-trans-retinol in hairless mouse skin.

  1987cites this paper
• Retinoids and epidermal growth factor alter embryonic mouse palatal epithelial and mesenchymal cell differentiation in organ culture.

  1987cites this paper