Kirkpatrick D L, King K M, Abu Sa'da I, Kelln R A, Richardson M E, Siemann D W
Department of Chemistry, University of Regina, Saskatchewan, Canada.
Anticancer Drugs. 1992 Dec;3(6):651-8. doi: 10.1097/00001813-199212000-00015.
A disulfide, n-butyl 2-imidazolyl disulfide (III-2), recently reported to be more toxic to EMT6 tumor cells under hypoxia has also been shown to be preferentially toxic to KHT/iv cells under hypoxia with an IC90 value 3-fold lower versus that measured in air. The IC90 values for both cell lines were markedly affected when the pHe was decreased. Uptake studies revealed that the disulfide is metabolized at the cell membrane with only one of the metabolites, n-butanethiol, being taken up into the cell. There were no differences in the amount of uptake under oxia or hypoxia. Investigation of potential membrane damage revealed that III-2 was a mixed inhibitor of the enzyme Na+,K(+)-ATPase, from isolated plasma membrane. DNA damage, when examined using plasmid DNA in the absence or presence of glutathione, was absent. Minor single-strand breaks to EMT6 DNA could only be observed following exposure to III-2 at the highest concentrations tested, with no differences observed between treatments in air or under hypoxia.
一种二硫化物，正丁基2 - 咪唑基二硫化物（III - 2），最近报道在缺氧条件下对EMT6肿瘤细胞毒性更大，在缺氧条件下对KHT/iv细胞也显示出优先毒性，其IC90值比在空气中测量的值低3倍。当细胞外pH值降低时，两种细胞系的IC90值均受到显著影响。摄取研究表明，该二硫化物在细胞膜处发生代谢，只有一种代谢产物正丁硫醇被摄取到细胞内。在有氧或缺氧条件下摄取量没有差异。对潜在膜损伤的研究表明，III - 2是分离的质膜中Na +,K(+) - ATP酶的混合抑制剂。在不存在或存在谷胱甘肽的情况下使用质粒DNA检测时，未发现DNA损伤。仅在测试的最高浓度下暴露于III - 2后，才能观察到EMT6 DNA的轻微单链断裂，在空气或缺氧处理之间未观察到差异。
