A comparative study of the induction of epidermal hyperplasia by natural and synthetic retinoids.
A comparative study of the induction of epidermal hyperplasia by natural and synthetic retinoids.
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发表时间：
1986-04
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通讯作者：
M. Connor;R. Ashton;N. Lowe
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作者：
M. Connor;R. Ashton;N. Lowe
类维生素A是表皮增生的有效诱导剂。在本研究中，比较了各种类维生素A诱导表皮增生的能力。将13种类维生素A和β-胡萝卜素在丙酮溶剂中局部应用于无毛小鼠的背部皮肤，并测量诱导增生的剂量反应和时间过程。峰值增生发生在单次局部给药后4 - 5天，并且由远低于产生皮肤毒性的大体或组织学体征的剂量诱导。增生的诱导具有剂量依赖性，表皮细胞层的数量最初与剂量的对数成比例增加，然后趋于平稳，或者在某些情况下减少，之后剂量的进一步增加与总体和组织学毒性的出现相关。测定初始增加相的斜率，并将效价表示为表皮细胞层数量增加50%的剂量。全反式维A酸及其类似物、阿维A酯及其游离酸、（E）-4 [2-（5，6，7，8-四氢-5，5，8，8-四甲基-2-萘基）-1-丙烯基]-苯甲酸（芳维A酸）衍生物、视黄醇和视黄醛产生细胞层数量的增加与剂量的对数成正比。脱羧的（E）-4-[2-（5，6，7，8-四氢-5，5，8，8-四甲基-2-萘基-1-丙烯基]-苯甲酸（视黄酸的顺式锁定芳基三烯衍生物）和β-胡萝卜素无活性。当类维生素A经口给药时，观察到类似的时间过程。该系统中类维生素A的相对效力显示出与其他体内和体外测定中测量的生物活性所报告的趋势相似的趋势。
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.