GLUTATHIONE AS A CELLULAR DEFENSE AGAINST ARSENITE TOXICITY IN CULTURED CHINESE-HAMSTER OVARY CELLS

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.