Bishayee A, Chatterjee M
Department of Pharmaceutical Technology, Jadavpur University, Calcutta, India.
Br J Cancer. 1995 Jun;71(6):1214-20. doi: 10.1038/bjc.1995.236.
The chemoprotective effect of vanadium, a dietary micronutrient, against chemically induced hepatocarcinogenesis in rats was investigated. Initiation was performed by a single intraperitoneal injection of diethylnitrosamine (DENA; 200 mg kg-1) followed by promotion with phenobarbital (0.05%) in the diet. Supplementary vanadium (0.5 p.p.m.) in the drinking water was provided ad libitum throughout the experiment, before the initiation or during the promotion period. At the end of the study (20 weeks), vanadium supplementation throughout the experiment reduced the incidence (P < 0.01), total number and multiplicity (P < 0.001) and altered the size distribution of visible persistent nodules (PNs) as compared with DENA control animals. Mean nodular volume (P < 0.05) and nodular volume as a percentage of liver volume (P < 0.01) were also attenuated following long-term vanadium treatment. It also caused a large decrease in the number (P < 0.001) and surface area (P < 0.01) of gamma-glutamyltranspeptidase (GGT)-positive hepatocyte foci and in the labelling index (P < 0.001) of focal cells, coupled with increased (P < 0.01) remodelling. The activity of GGT, measured quantitatively, was found to be significantly less in the PNs (P < 0.001) and non-nodular surrounding parenchyma (P < 0.01) of vanadium-supplemented rats. The anticarcinogenic effect of vanadium was also reflected in the histopathological analysis of liver sections that showed a well-maintained hepatocellular architecture as compared with DENA control. Similar results were observed when vanadium was given only before the initiation. However, supplementation of vanadium during the promotion period did not result in significant alterations of these parameters. Our results, thus, strongly suggest that vanadium may have a unique anti-tumour potential which is primarily exerted on the initiation phase and only secondarily on the promotion stage.
研究了膳食微量营养素钒对化学诱导的大鼠肝癌发生的化学保护作用。通过单次腹腔注射二乙基亚硝胺（DENA；200 mg/kg-1）启动肝癌发生，随后在饮食中用苯巴比妥（0.05%）进行促癌。在整个实验过程中，无论是在启动前还是促癌期，均随意提供含补充钒（0.5 ppm）的饮用水。在研究结束时（20周），与DENA对照动物相比，整个实验过程中补充钒降低了发病率（P < 0.01）、总数和多灶性（P < 0.001），并改变了可见持续性结节（PNs）的大小分布。长期钒处理后，平均结节体积（P < 0.05）和结节体积占肝脏体积的百分比（P < 0.01）也有所降低。它还导致γ-谷氨酰转肽酶（GGT）阳性肝细胞灶的数量（P < 0.001）和表面积（P < 0.01）以及灶性细胞的标记指数（P < 0.001）大幅下降，同时重塑增加（P < 0.01）。定量测量发现，补充钒的大鼠的PNs（P < 0.001）和非结节性周围实质（P < 0.01）中的GGT活性明显较低。钒的抗癌作用还反映在肝脏切片的组织病理学分析中，与DENA对照相比，肝细胞结构保持良好。仅在启动前给予钒时也观察到了类似结果。然而，在促癌期补充钒并未导致这些参数发生显著变化。因此，我们的结果强烈表明，钒可能具有独特的抗肿瘤潜力，主要作用于启动阶段，其次才作用于促癌阶段。
