Kralovánszky J, Jenkins W L, Greenwell A, Melnick R L
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Res Commun Chem Pathol Pharmacol. 1989 May;64(2):299-316.
Intestinal cells were isolated from male Fischer 344 rats by the collagenase portal vein perfusion procedure and evaluated for direct effects of cis-diamminedichloroplatinum (CDDP) and ethylacrylate (EtAc) on metabolic activities. Specific activities of marker enzymes of intestinal crypt and villus cells indicated that the preparations contained predominantly villus cells. Cell viability was generally greater than 90%, and was maintained longest when the cells were suspended in M-199 medium supplemented with 1% BSA. EtAc, an industrial intermediate which is toxic to tissues which are directly exposed to this chemical, had no apparent effect on rates of glucose metabolism or protein synthesis in suspensions of the isolated intestinal cells. These metabolic processes, however, were inhibited by the anticancer agent, CDDP; the mechanism of cytotoxicity of CDDP may therefore be due to interference with intermediary metabolism. The present studies indicate that isolated intestinal cell suspensions may be useful in examining direct and immediate effects of chemicals which are toxic to the intestinal epithelium, and in evaluating potential cytotoxic effects of CDDP analogs which have been developed.
通过胶原酶门静脉灌注法从雄性Fischer 344大鼠中分离出肠道细胞，并评估顺二氯二氨铂（CDDP）和丙烯酸乙酯（EtAc）对其代谢活性的直接影响。肠道隐窝和绒毛细胞标记酶的比活性表明，所制备的细胞主要为绒毛细胞。细胞活力一般大于90%，当细胞悬浮于补充有1%牛血清白蛋白的M-199培养基中时，活力维持时间最长。EtAc是一种工业中间体，对直接接触该化学物质的组织有毒性，但对分离出的肠道细胞悬液中的葡萄糖代谢率或蛋白质合成没有明显影响。然而，抗癌药物CDDP抑制了这些代谢过程；因此，CDDP的细胞毒性机制可能是由于干扰了中间代谢。目前的研究表明，分离出的肠道细胞悬液可用于检测对肠道上皮有毒性的化学物质的直接和即时影响，以及评估已开发的CDDP类似物的潜在细胞毒性作用。
