Studies on the separation and mechanism of albumin synthesis in albumin-positive cells derived from Nagase analbuminemic rats (NAR).

长酶无球蛋白血症大鼠（NAR）的特点是血清白蛋白极低，高脂血症，生长繁殖正常。然而，少量白蛋白阳性肝细胞分布在肝脏中。我们观察到由于衰老、部分肝切除术、CCl4诱导的肝硬化和给药3′-Me-DAB后的肿瘤改变导致的NAR中白蛋白阳性细胞的发生模式。这些发生模式与肝细胞再生密切相关。为了研究白蛋白阳性细胞，我们尝试用percol -density gradient离心分离这些细胞。第三部分白蛋白阳性细胞相对积累，但分离出来的细胞不稳定，不能应用该分析方法。因此，需要从NAR中提取白蛋白阳性细胞系。给予3'- me - DAB约25周后可形成混合型肝癌（髓样、囊样和增殖性胆管样），至今已建立4种不同类型的细胞系。所建立的细胞系具有以下特点：1)在培养皿中呈表皮样，2)倍增时间：15 ~ 30小时，3)染色体数：60 ~ 120,4)染色体类型：大鼠衍生型。免疫组化染色显示培养细胞中AFP阳性部分，但几乎未见白蛋白阳性部分。通过长期培养和添加肝细胞刺激因子，在细胞系中诱导白蛋白阳性细胞的研究一直在继续。

Nagase analbuminemic rat (NAR) is characterized by very low serum albumin, hyperlipideamia, and normal rate of growth and propagation. however, a small number of albumin positive hepatocytes is distributed in the liver. We observed occurring modes of albumin positive cells in NAR due to aging, partial hepatectomy, and cirrhosis induced by CCl4 and neoplastic change after administration of 3'-Me-DAB. Those occurring modes had strong relation to regeneration of hepatocytes. In the aim to investigate albumin positive cells, we tried to separate these cells using percoll-density gradient centrifugation. Albumin positive cells relatively accumulated in the third fraction, however, these cells separated were not stable for applying the analytical method. Therefore, albumin positive cell line derived from NAR was required. After administration of 3'-Me- DAB, about 25 weeks later mixed type of hepatomas ( medullary, cystic and proliferated bile duct-like) were developed and 4 types of different cell lines were established until now. Established cell line showed several characteristics as follows: 1) epidermal-like shape in culture dish, 2) doubling time: 15-30 hr, 3) chromosome number: 60-120, 4) chromosome type: rat derived type. Immunohistochemical staining revealed AFP positive portion in cultured cells, but, albumin positive portion was hardly detected.Studies on the induction of albumin positive cells in cell lines have been continued by long-term culture and addition of hepatocyte stimulating factors.