He R K, Gascon-Barré M
Centre de Recherche Clinique André-Viallet, Hôpital Saint-Luc, Montréal, Canada.
J Pharmacol Exp Ther. 1997 Apr;281(1):464-9.
Although 1,25-dihydroxyvitamin D3 has been shown to promote the differentiation of cancer cells and cell lines in vitro, its protective effect against a chemical insult known to induce neoplastic growth in vivo has not been evaluated. The aim of this study was to investigate, in vivo, the influence of the vitamin D status on the early response to an insult known to induce morphological and functional changes leading to hepatocarcinogenesis. The influence of vitamin D status on the susceptibility of rat liver to carcinogenesis was studied after the administration of diethylnitrosamine and 2-acetylaminofluorene, in association with a partial hepatectomy (Solt-Farber protocol), to normal or vitamin D-depleted rats. Preneoplastic foci (gamma-glutamyltranspeptidase-positive and glucose-6-phosphatase-negative) appeared in both groups of animals as early as 1 week after 2-acetylaminofluorene withdrawal and continued to increase during the subsequent weeks. Livers from vitamin D-depleted rats exhibited a significant increase in the number of foci over that observed in normal rats at weeks 1 and 5 after 2-acetylaminofluorene withdrawal. However, the main effect of vitamin D depletion was on focus size, which was found to be significantly greater in vitamin D-depleted rat livers at weeks 2 to 6; focus area (volume fraction) was also found to be consistently larger in livers of vitamin D-depleted rats than in those of normal rats. Labeling of oval cells, a cell compartment possibly associated with the repopulation of the liver parenchyma, was significantly reduced by vitamin D depletion. Control rat livers of both groups showed normal liver histology, and no foci, nodules or oval cells were detected in either group. The present data suggest that vitamin D depletion leads to increased in vivo susceptibility to chemicals known to induce hepatocarcinogenesis. Long-term studies must be conducted to evaluate the effect of vitamin D status on the evolution of preneoplastic foci into frank hepatocellular carcinoma.
尽管1,25 - 二羟基维生素D3在体外已被证明可促进癌细胞和细胞系的分化，但其对已知能在体内诱导肿瘤生长的化学损伤的保护作用尚未得到评估。本研究的目的是在体内研究维生素D状态对已知能诱导导致肝癌发生的形态和功能变化的损伤的早期反应的影响。在给正常或维生素D缺乏的大鼠施用二乙基亚硝胺和2 - 乙酰氨基芴并结合部分肝切除术（索尔 - 法伯方案）后，研究了维生素D状态对大鼠肝脏致癌易感性的影响。早在停用2 - 乙酰氨基芴后1周，两组动物中均出现了癌前病灶（γ - 谷氨酰转肽酶阳性且葡萄糖 - 6 - 磷酸酶阴性），并在随后几周持续增加。在停用2 - 乙酰氨基芴后第1周和第5周，维生素D缺乏大鼠肝脏中的病灶数量比正常大鼠显著增加。然而，维生素D缺乏的主要影响在于病灶大小，发现在停用2 - 乙酰氨基芴后第2至6周，维生素D缺乏大鼠肝脏中的病灶明显更大；维生素D缺乏大鼠肝脏中的病灶面积（体积分数）也始终大于正常大鼠肝脏中的病灶面积。维生素D缺乏显著减少了卵圆细胞（一种可能与肝实质再填充相关的细胞区室）的标记。两组对照大鼠肝脏均显示正常肝脏组织学，两组中均未检测到病灶、结节或卵圆细胞。目前的数据表明，维生素D缺乏会导致体内对已知能诱导肝癌发生的化学物质的易感性增加。必须进行长期研究以评估维生素D状态对癌前病灶演变为明显肝细胞癌的影响。
