Temmink J H, Bruggeman I M, van Bladeren P J
Arch Toxicol. 1986 Jul;59(2):103-10. doi: 10.1007/BF00286732.
Since allyl isothiocyanate has been reported to be a bladder carcinogen and benzyl isothiocyanate is a known anti-carcinogen, it is important to know the mode of their cytotoxic action. This was investigated in a RL-4 hepatocyte cell line by studying the morphological effects of increasing concentrations of the isothiocyanates and their glutathione and cysteine conjugates. These effects were compared with those induced by tert-butylhydroperoxide which supposedly has its primary effect upon the cytosolic glutathione status and thus upon the integrity of Ca2+-sequestrating mitochondria. The results agree with the previously postulated role of conjugation in the exposure of cells to isothiocyanates: Conjugates show effects similar to those produced by the free parent compounds because conjugates release free isothiocyanates in aqueous solution. The cytomorphological effects increase in a more or less dose-dependent manner with increasing concentrations of isothiocyanate or exposure time. Probably due to increased exposure, suspended RL-4 cells are more sensitive to the toxic action than cells growing on a substrate. No qualitative differences were found between the effects of allyl and benzyl isothiocyanate, indicating that their different effects in vivo are perhaps related to organ-specific differences in equilibrium between the conjugated and unconjugated forms of the test substances. The first cytomorphological effects of isothiocyanates consist of surface blebbing (zeiosis) and swelling of dictyosomal cisternae. At higher concentrations swelling extends to vesicles of endoplasmic reticulum. Mitochondria are not affected until the cells reach the necrotic phase of injury.(ABSTRACT TRUNCATED AT 250 WORDS)
由于烯丙基异硫氰酸酯已被报道为膀胱致癌物，而苄基异硫氰酸酯是一种已知的抗癌剂，因此了解它们的细胞毒性作用模式很重要。通过研究异硫氰酸酯及其谷胱甘肽和半胱氨酸共轭物浓度增加时的形态学效应，在RL - 4肝细胞系中对此进行了研究。将这些效应与叔丁基过氧化氢诱导的效应进行比较，叔丁基过氧化氢据推测主要作用于胞质谷胱甘肽状态，进而作用于钙隔离线粒体的完整性。结果与先前假设的共轭作用在细胞接触异硫氰酸酯中的作用一致：共轭物显示出与游离母体化合物产生的效应相似的效应，因为共轭物在水溶液中释放出游离异硫氰酸酯。随着异硫氰酸酯浓度或暴露时间的增加，细胞形态学效应或多或少呈剂量依赖性增加。可能由于暴露增加，悬浮的RL - 4细胞比在底物上生长的细胞对毒性作用更敏感。烯丙基异硫氰酸酯和苄基异硫氰酸酯的效应之间未发现定性差异，这表明它们在体内的不同效应可能与受试物质共轭和非共轭形式之间平衡的器官特异性差异有关。异硫氰酸酯的最初细胞形态学效应包括表面起泡（泡化）和高尔基体潴泡肿胀。在较高浓度下，肿胀扩展到内质网小泡。直到细胞达到损伤的坏死阶段，线粒体才会受到影响。（摘要截短于250字）
