Freshly isolated renal cells as a experimental model system for studying the chemically induced renal injury.

为了建立新鲜分离的肾细胞作为毒性评价的体外实验方法，我们对Jones(1979)的方法进行了改进，获得了高活性(~gt；95%)和高产量(Ca&lt；10~8细胞/只)的细胞。该制剂具有较高的酶活性，主要存在于近端肾小管上皮细胞中。大多数细胞与上皮细胞特异性的单抗结合。这些结果表明，大多数细胞起源于肾脏的这一区域。甲状旁腺激素使肾细胞内cAMP含量增加，8-苯胺基-1-萘磺酸盐处理的细胞膜上存在有机阴离子载体。肾细胞的氨基比林代谢活性约为肝细胞的0.4%。化学物质的毒性作用是：1)直接作用剂，如&lt；HgCl2&gt；，&lt；虽然GSH可抑制双硫仑的作用，但半胱氨酸和GSH不能完全抑制&lt；CdCl2和Gt；的作用。2)庆大霉素对细胞GSH含量无明显影响，但阿霉素可降低细胞GSH含量。3)已知由细胞色素T代谢激活的环磷酰胺和扑热息痛。P-450连接药物代谢系统，无毒性作用。4)烯丙醇对雌性大鼠有明显的毒性作用，其乙醇脱氢酶活性高于雄性大鼠，提示肾细胞制片可用于化学物质急性毒性机制的研究。

For the purpous to establish freshly isolated renal cells as a in vitro test method of toxicity evaluation, we improved the method of Jones'(1979) and obtained the cells with high viability ( >95%) and yield (Ca <10^8> cells/rat). This preparation had a high activity of the enzymes which existed predominantly in proximal renal tubular epithelial cells. Most of the cells bound with monoclonal antibody which was specific to the epithelial cells. These results indicated that most of the cells were originated from this region of the kidneys. Parathyroid hormon increased cAMP content of the renal cells.Carriar of the organic anion was shown to exist in the cell membrane using 8-anilino 1-naphthalene sulfornate. Aminopyrine metabolizing activities of the renal cells were about 0.4% of those of hepatocytes. Toxic effects of chemicals were : 1 ) Direct acting agents, such as <HgCl_2> , <CdCl_2> , and disulfiram, caused the loss of viability of the cells. Although the effects of disulfiram were inhibited by GSH, those of <CdCl_2> were not inhibited completely by cysteine and GSH. 2 ) Effects of gentamycin were not observed, but adriamycin decreased the GSH content of the cells. 3 ) Cyclophosphamide and paracetamol, which were known to be activated metabolically by cyt. P-450 linked drug metabolizing system, did not have toxic effects. 4 ) Toxicity of allyl alcohol were marked in female rats, in which activity of alcohol dehydrogenase were higher than in male rats.These results indicated that the renal cell preparation could be used to study the mechanism of acute toxicity of chemicals.