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United States Department of Agriculture

Agricultural Research Service

Title: The Effect of Arsenic on the Selenium-Induced Cell Death Pathway

Author
item Zeng, Huawei

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: December 10, 2000
Publication Date: March 7, 2001
Citation: Zeng, H. 2001. The effect of arsenic on the selenium-induced cell death pathway [abstract]. The Federation of American Societies for Experimental Biology Journal. 15:A604.

Technical Abstract: Selenium, an essential trace element for humans, has been shown to have anti-cancer effects at doses higher than that of the nutritional requirement. Arsenic, possibly essential ultra-trace element, has been shown to be effective against leukemia. Anti-cancer effects of selenium and arsenic have been related to their ability to induce apoptosis. Because humans are exposed to diverse trace elements simultaneously, it is important to learn their inter-relationship. In this study, we first demonstrate that sodium selenite (Na2SeO3) causes apoptosis at 3 uM and necrosis at high concentrations (> 3 uM) in HL-60 cells. Similarly, both sodium arsenite (NaAsO2) at 50 uM and sodium arsenate (Na2HAsO4) at 500 uM induce apoptosis, and necrosis at higher concentrations (>50 uM and >500 uM respectively) in HL-60 cells. Arsenic, but not selenium, enhances AP-1 DNA-binding activity. This finding indicates different mechanisms through which apoptosis is induced by these two elements. Interestingly, we observed that HL-60 cell necrosis induced by a high concentration (> 3 uM) of selenium was essentially inhibited by arsenic (50 uM of NaAsO2 or 500 uM of Na2HAsO4), which resulted in a net effect of apoptosis. Because AP- 1 DNA binding activity was not induced in the presence of a combination of necrotic amount of selenium and apoptotic amount of arsenic, the observed apoptosis apparently was through the mechanism used by selenium. Our results suggest for the first time that the toxic necrotic effect of selenium can be neutralized by arsenic at the cellular level.

Last Modified: 8/27/2014
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