Next Article in Journal / Special Issue
Perturbation of the Developmental Potential of Preimplantation Mouse Embryos by Hydroxyurea
Previous Article in Journal / Special Issue
Basic Apoptotic Mechanisms of Lead Toxicity in Human Leukemia (Hl-60) Cells
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
Received: 8 January 2010 / Revised: 26 February 2010 / Accepted: 3 April 2010 / Published: 28 April 2010

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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
EndNote
MDPI and ACS Style

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.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here

Comments

Cited By

[Return to top]
Int. J. Environ. Res. Public Health EISSN 1660-4601 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert