Lützow-Holm C, De Angelis P, Clausen O P
Institute of Pathology, University of Oslo, National Hospital, Rikshospitalet, Norway.
J Investig Dermatol Symp Proc. 1996 Apr;1(1):54-9.
Calcitriol and its analogs are used in the treatment of psoriasis and may also induce epidermal proliferation, hyperplasia, and irritation in normal skin by an unknown mechanism. The effects of a single dose of calcitriol and the 20-epi-vitamin D3 analog KH 1060 were therefore examined by performing 5-bromo-2'-deoxyuridine (BrdU) pulse chase labeling experiments in unperturbed hairless mouse epidermis in vivo. One cohort of basal cells was exposed to calcitriol mainly during the S phase, whereas another cohort in G1/G0 phase was stimulated by calcitriol or KH 1060 into S phase 16 h before BrdU labeling. Basal keratinocytes were isolated from epidermis and analyzed by bivariate BrdU/DNA flow cytometry. Calcitriol and KH 1060 induced similar proliferative responses, with a peak of cells in S phase at about 16 h after drug applications. The cohorts in G1/G0 phase at the time of drug application displayed a reduced cell cycle, whereas the cohort of cells in S phase at the time of calcitriol application did not show a similar reduction. The proliferation kinetics observed are thus different from those seen after retinoic acid treatment, since retinoic acid did not reduce the cell cycle time under similar conditions. Reduction of cell cycle time may be a characteristic effect of calcitriol and KH 1060, similar to that seen after other hyperplasiogens. The results also indicate that the drugs exert differential effects on cells depending on the cells' position in the cell cycle during treatment.
骨化三醇及其类似物用于治疗银屑病，也可能通过未知机制在正常皮肤中诱导表皮增殖、增生和刺激。因此，通过在未受干扰的无毛小鼠表皮中进行体内5-溴-2'-脱氧尿苷（BrdU）脉冲追踪标记实验，研究了单剂量骨化三醇和20-表维生素D3类似物KH 1060的作用。一组基底细胞主要在S期暴露于骨化三醇，而另一组处于G1/G0期的细胞在BrdU标记前16小时被骨化三醇或KH 1060刺激进入S期。从表皮中分离出基底角质形成细胞，并通过双变量BrdU/DNA流式细胞术进行分析。骨化三醇和KH 1060诱导了相似的增殖反应，给药后约16小时S期细胞达到峰值。给药时处于G1/G0期的细胞群显示细胞周期缩短，而骨化三醇给药时处于S期的细胞群未显示类似的缩短。因此，观察到的增殖动力学与维甲酸治疗后的不同，因为在相似条件下维甲酸并未缩短细胞周期时间。细胞周期时间的缩短可能是骨化三醇和KH 1060的特征性作用，类似于其他增生剂作用后的情况。结果还表明，在治疗期间，这些药物对细胞的作用因细胞在细胞周期中的位置而异。
