Abdel-Rahman S Z, Nouraldeen A M, Abo-Elwafa A A, Ahmed A E
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0605, USA.
Toxicol In Vitro. 1994 Apr;8(2):139-43. doi: 10.1016/0887-2333(94)90176-7.
Isolated rat intestinal epithelial cells (IEC) were used to investigate the mechanism(s) of acrylonitrile (VCN)-induced gastro-intestinal damage. The isolated cells were 93% structurally intact for 60 min, as indicated by trypan blue exclusion. Uridine uptake by isolated IEC was linear from 6-20 min, after which a steady state was reached for up to 40 min. Exposure of isolated IEC to various concentrations of VCN reduced the ability of the cells to take up uridine in a concentration-dependent manner. A concentration of 82 mum VCN inhibited the [(3)H]uridine uptake of the cells by 50% (IU(50)). A time-course study indicated that the maximal inhibition of uridine uptake occurred at 15 min after exposure to VCN. The VCN-induced inhibition of uridine uptake was found to be reversible. IEC exposed to two sublethal doses of VCN (41 and 82 mum) for 15 min regained normal uridine uptake activity within 50 min after removal of VCN. The present study provides a sensitive approach for the detection and evaluation of cytotoxic risk of sublethal doses of the gastro-intestinal toxin VCN using IEC as target cells. The observed in vitro cytotoxicity of sublethal doses of VCN will be used to investigate further the mechanism of VCN-induced gastro-intestinal damage.
分离的大鼠肠上皮细胞（IEC）被用于研究丙烯腈（VCN）诱导的胃肠道损伤机制。如台盼蓝排斥试验所示，分离的细胞在60分钟内结构完整性达93%。分离的IEC摄取尿苷在6 - 20分钟呈线性，之后在长达40分钟内达到稳态。将分离的IEC暴露于不同浓度的VCN会以浓度依赖的方式降低细胞摄取尿苷的能力。82 μmol的VCN浓度可使细胞对[³H]尿苷的摄取抑制50%（半数抑制浓度（IU₅₀））。一项时间进程研究表明，暴露于VCN后15分钟尿苷摄取受到最大抑制。发现VCN诱导的尿苷摄取抑制是可逆的。暴露于两个亚致死剂量VCN（41和82 μmol）15分钟的IEC在去除VCN后50分钟内恢复正常的尿苷摄取活性。本研究提供了一种以IEC作为靶细胞检测和评估亚致死剂量胃肠道毒素VCN细胞毒性风险的灵敏方法。观察到的亚致死剂量VCN的体外细胞毒性将用于进一步研究VCN诱导的胃肠道损伤机制。
