Huang H, Huang C F, Wu D R, Jinn C M, Jan K Y
Institute of Radiation Biology, National Tsing-Hua University, Hsinchu, Taiwan, Republic of China.
Toxicology. 1993 May 24;79(3):195-204. doi: 10.1016/0300-483x(93)90211-a.
The cytotoxic effect of arsenite seems to be inversely related to the intracellular glutathione (GSH) content, and GSH seems to facilitate the metabolism of arsenic in cell. Arsenite is also known to induce chromosome aberration, to enhance the cytotoxicity and clastogenicity of ultraviolet (UV) light, and to inhibit UV-induced DNA repair. We have investigated whether these toxic effects of arsenite and the cellular arsenic content are also modulated by the intracellular GSH. A 2-h pretreatment of the cultured ovary (CHO) cells with GSH reduced the clastogenicity and cytotoxicity of arsenite. The enhancing effects of arsenite on chromosome aberrations and cell destruction induced by UV were also reduced by a 2-h pretreatment with GSH. The inhibitory effect of arsenite on the strand-break rejoining during UV-induced DNA repair was reduced by GSH pretreatment and was enhanced by pretreatment with buthionine sulfoximine, which is known to deplete the cellular GSH. The cellular arsenic content was reduced by GSH pretreatment and increased by buthionine sulfoximine pretreatment. GSH given before or simultaneously with arsenite, effectively reduced the clastogenicity and coclastogenicity of arsenite. GSH given after treatment with arsenite decreased the cellular arsenic content, and increased the cell survival, but did not reduce the clastogenicity or the coclastogenicity of arsenite.
亚砷酸盐的细胞毒性作用似乎与细胞内谷胱甘肽（GSH）含量呈负相关，并且GSH似乎有助于细胞内砷的代谢。已知亚砷酸盐可诱导染色体畸变，增强紫外线（UV）的细胞毒性和致断裂性，并抑制紫外线诱导的DNA修复。我们研究了亚砷酸盐的这些毒性作用以及细胞内砷含量是否也受细胞内GSH的调节。用GSH对培养的卵巢（CHO）细胞进行2小时预处理可降低亚砷酸盐的致断裂性和细胞毒性。用GSH进行2小时预处理也可降低亚砷酸盐对紫外线诱导的染色体畸变和细胞破坏的增强作用。GSH预处理可降低亚砷酸盐对紫外线诱导的DNA修复过程中链断裂重新连接的抑制作用，而用已知可耗尽细胞内GSH的丁硫氨酸亚砜胺预处理则可增强该抑制作用。GSH预处理可降低细胞内砷含量，而丁硫氨酸亚砜胺预处理则可增加细胞内砷含量。在亚砷酸盐之前或同时给予GSH可有效降低亚砷酸盐的致断裂性和共断裂性。在亚砷酸盐处理后给予GSH可降低细胞内砷含量，并提高细胞存活率，但不会降低亚砷酸盐的致断裂性或共断裂性。
