Mason B, Ghanee N, Haigh W G, Lee S P, Oda D
Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Washington, Seattle, USA.
Anticancer Res. 1999 Nov-Dec;19(6B):5469-74.
There is experimental and epidemiological evidence that antioxidant vitamins can inhibit carcinogenesis. Since immortalization by Human Papilloma Virus (HPV) is one possible early step towards carcinogenesis in oral epithelia, we studied the differential effect of vitamins A, C and E on HPV-immortalized oral epithelial cells (IHGK) as compared to the normal counterpart. The dose response was determined by morphology, cell cycle by flow cytometry, and growth curve by cell number. The optimum dose in terms of inhibitory effect vs. toxicity was determined for each vitamin by morphology. Optimum doses were: vitamin A--1.4 x 10(-5) M, vitamin C--10(-3) M, and vitamin E--10(-6) M for both HPV-immortalized and normal cells. Growth curve showed reduction of proliferation by all three vitamins, with vitamins A and E more effective than C for both cell types. Flow cytometry showed that vitamins A and E reduced the percentage of cells at G2 phase of cell cycle and indicated arrest in the S phase. This effect was greatest in the immortalized cells with a 50% and 35% decrease of G2 for vitamins A and E respectively, whereas the normal counterpart showed a 48% decrease for A and a 12% increase for E. By organotypic culture, the morphology was not markedly different between the vitamin-treated and the control cells, except for a slight increase in the keratinization of normal cells with vitamin A. Also noted was a reduction in number of cell layers from five layers or more for controls to only one or two for vitamin E. In conclusion, we have demonstrated that the antioxidant vitamins inhibit proliferation, and show a preferential effect on IHGK cells.
有实验和流行病学证据表明抗氧化维生素可抑制癌症发生。由于人乳头瘤病毒（HPV）导致的永生化是口腔上皮细胞发生癌变的一个可能早期步骤，我们研究了维生素A、C和E对HPV永生化口腔上皮细胞（IHGK）与正常对应细胞的不同作用。通过形态学确定剂量反应，通过流式细胞术确定细胞周期，通过细胞数量确定生长曲线。通过形态学为每种维生素确定抑制作用与毒性方面的最佳剂量。最佳剂量为：维生素A——1.4×10⁻⁵ M，维生素C——10⁻³ M，维生素E——10⁻⁶ M，对HPV永生化细胞和正常细胞均如此。生长曲线显示所有三种维生素均使增殖减少，对于两种细胞类型，维生素A和E比维生素C更有效。流式细胞术显示维生素A和E降低了细胞周期G2期的细胞百分比，并表明细胞停滞在S期。这种作用在永生化细胞中最为明显，维生素A和E分别使G2期减少50%和35%，而正常对应细胞中维生素A使G2期减少48%，维生素E使G2期增加12%。通过器官型培养，维生素处理组和对照组细胞的形态没有明显差异，只是维生素A处理的正常细胞角化略有增加。还注意到细胞层数从对照组的五层或更多减少到维生素E处理组的仅一或两层。总之，我们已证明抗氧化维生素抑制增殖，并对IHGK细胞显示出优先作用。
