Marionnet A V, Lizard G, Chignol M C, Chardonnet Y, Schmitt D
INSERM U346 Pavillon, R, Hôpital E. Herriot, Lyon, France.
Anticancer Res. 1996 Jan-Feb;16(1):257-67.
In humans, cyclosporin A (CsA) avoids organ allograft rejection but induces skin carcinomas after long term immunosuppressive treatment; some of these lesions contain human papillomavirus (HPV) DNA. Interferon-gamma (IFN-gamma) is sometimes used in local treatment of persistent or recurrent lesions in normal population. In vivo, both drugs have an effect on keratinocytes which remains unclear. Therefore, their effect was studied on in vitro models of normal or HPV-transformed epithelial cell cultures. After exposure of proliferating cells for 1-3 days to 0.5-16 micrograms/ml CsA and 5-160 U/ml IFN-gamma, no cytotoxicity was observed; cell growth was inhibited; cell morphology was altered with CsA and cytoplasmic vacuoles were seen in some cells. Changes in the cell cycle were mainly obtained after treatment with 8 micrograms/ml CsA or 160 U/ml IFN-gamma, with an accumulation in S-phase especially in HPV-transformed cells. Thus, CsA and IFN-gamma affected, normal and HPV-transformed epithelial cells, differently.
在人类中,环孢素A(CsA)可避免器官移植排斥反应,但在长期免疫抑制治疗后会诱发皮肤癌;其中一些病变含有人类乳头瘤病毒(HPV)DNA。干扰素-γ(IFN-γ)有时用于正常人群中持续性或复发性病变的局部治疗。在体内,这两种药物对角质形成细胞均有影响,但其机制尚不清楚。因此,研究了它们对正常或HPV转化的上皮细胞培养体外模型的影响。将增殖细胞暴露于0.5-16微克/毫升的CsA和5-160单位/毫升的IFN-γ中1-3天,未观察到细胞毒性;细胞生长受到抑制;CsA使细胞形态发生改变,部分细胞可见细胞质空泡。细胞周期的变化主要在使用8微克/毫升的CsA或160单位/毫升的IFN-γ处理后出现,尤其是在HPV转化的细胞中S期出现积累。因此,CsA和IFN-γ对正常和HPV转化的上皮细胞的影响有所不同。