Tanii H, Miki N, Hayashi M, Hashimoto K
Department of Hygiene, School of Medicine, Kanazawa University, Japan.
Arch Toxicol. 1988;61(4):298-305. doi: 10.1007/BF00364853.
Cytotoxicity of acrylamide and related compounds to mouse neuroblastoma N18TG-2 and rat Schwannoma RT4 cells was studied. Of nine test chemicals, acrylamide and N-hydroxymethylacrylamide were most toxic compared with others on the basis of ED50 value. Observation under phase-contrast microscopy revealed that in N18TG-2 acrylamide produced both degeneration of the cells and inhibition of cell growth, and that in RT4 it produced only inhibition of cell growth without causing any marked morphological changes. Dibutyryl cyclic AMP (dBcAMP) reduced the cytotoxicity of acrylamide to both types of cells on the basis of the dose-effect curve. Studies on the subcellular distribution of 14C-acrylamide incorporated showed that more than 90% of the total radioactivity was incorporated in the 15,000 g supernant fraction. Kinetics of acrylamide uptake by N18TG-2 cells showed that in the cells untreated with dBcAMP there were two binding sites with high and low affinity, and that after treatment with dBcAMP the site of high affinity disappeared. The situation was true for RT4 cells, the results indicating that the immature cells are more vulnerable to acrylamide than the mature cells.
研究了丙烯酰胺及相关化合物对小鼠神经母细胞瘤N18TG - 2细胞和大鼠雪旺细胞瘤RT4细胞的细胞毒性。在九种受试化学物质中,根据半数有效剂量(ED50)值,丙烯酰胺和N - 羟甲基丙烯酰胺比其他物质毒性更强。相差显微镜观察显示,在N18TG - 2细胞中,丙烯酰胺会导致细胞变性和细胞生长抑制,而在RT4细胞中,它仅抑制细胞生长,未引起任何明显的形态变化。基于剂量效应曲线,二丁酰环磷腺苷(dBcAMP)降低了丙烯酰胺对两种细胞的细胞毒性。对掺入的14C - 丙烯酰胺亚细胞分布的研究表明,总放射性的90%以上掺入到15,000g上清组分中。N18TG - 2细胞摄取丙烯酰胺的动力学表明,在未用dBcAMP处理的细胞中有两个高亲和力和低亲和力的结合位点,在用dBcAMP处理后,高亲和力位点消失。RT4细胞也是如此,结果表明未成熟细胞比成熟细胞对丙烯酰胺更敏感。