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Int. J. Environ. Res. Public Health 2010, 7(5), 2018-2032; doi:10.3390/ijerph7052018
Article

The Effects of Arsenic Trioxide on DNA Synthesis and Genotoxicity in Human Colon Cancer Cells

1,* , 2
,
2
,
2
 and
2
1 Molecular and Cellular Biology Research Laboratory, NIH-Center for Environmental Health, College of Science, Engineering and Technology, Jackson State University, 1400 JR Lynch Street, Box 18540, Jackson, MS 39217, USA 2 Molecular Toxicology Research Laboratory, NIH-Center for Environmental Health, College of Science, Engineering and Technology, Jackson State University, 1400 JR Lynch Street, Box 18540, Jackson, MS 39217, USA
* Author to whom correspondence should be addressed.
Received: 8 January 2010 / Revised: 26 February 2010 / Accepted: 3 April 2010 / Published: 28 April 2010
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Abstract

Colon cancer is the third leading cause of cancer-related deaths worldwide. Recent studies in our laboratory have demonstrated that arsenic trioxide is cytotoxic in human colon cancer (HT-29), lung (A549) and breast (MCF-7) carcinoma cells. The purpose of the present study is to investigate the effects of arsenic trioxide on DNA synthesis and the possible genotoxic effects on human colon cancer cells. HT-29 cells were cultured according to standard protocol, followed by exposure to various doses (0, 2, 4, 6, 8, 10, and 12 μg/mL) of arsenic trioxide for 24 h. The proliferative response (DNA synthesis) to arsenic trioxide was assessed by [3H]thymidine incorporation. The genotoxic effects of arsenic-induced DNA damage in a human colon cancer cell line was evaluated by the alkaline single cell gel electrophoresis. Results indicated that arsenic trioxide affected DNA synthesis in HT-29 cells in a biphasic manner; showing a slight but not significant increase in cell proliferation at lower levels of exposure (2, 4 and 6 µg/mL) followed by a significant inhibition of cell proliferation at higher doses (i.e., 8 and 10 µg/mL). The study also confirmed that arsenic trioxide exposure caused genotoxicity as revealed by the significant increase in DNA damage, comet tail-lengths, and tail moment when compared to non-exposed cells. Results of the [3H]thymidine incorporation assay and comet assay revealed that exposure to arsenic trioxide affected DNA synthesis and exhibited genotoxic effects in human colon cancer cells.
Keywords: Arsenic trioxide; HT-29 cells; [3H]thymidine incorporation assay; genotoxicity; comet assay Arsenic trioxide; HT-29 cells; [3H]thymidine incorporation assay; genotoxicity; comet assay
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Stevens, J.J.; Graham, B.; Walker, A.M.; Tchounwou, P.B.; Rogers, C. The Effects of Arsenic Trioxide on DNA Synthesis and Genotoxicity in Human Colon Cancer Cells. Int. J. Environ. Res. Public Health 2010, 7, 2018-2032.

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