title: The effects of arsenic trioxide on DNA synthesis and genotoxicity in human colon cancer cells.
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 microg/mL) of arsenic trioxide for 24 h. The proliferative response (DNA synthesis) to arsenic trioxide was assessed by [(3)H]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 microg/mL) followed by a significant inhibition of cell proliferation at higher doses (i.e., 8 and 10 microg/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 [(3)H]thymidine incorporation assay and comet assay revealed that exposure to arsenic trioxide affected DNA synthesis and exhibited genotoxic effects in human colon cancer cells.
authors.affiliation: Molecular and Cellular Biology Research Laboratory, NIH-Center for Environmental Health, College of Science, Engineering and Technology, Jackson State University, Jackson, MS 39217, USA. Jacqueline.j.stevens@jsums.edu
authors.forename: Jacqueline J
authors.initials: JJ
authors.lastname: Stevens
authors.forename: Barbara
authors.initials: B
authors.lastname: Graham
authors.forename: Alice M
authors.initials: AM
authors.lastname: Walker
authors.forename: Paul B
authors.initials: PB
authors.lastname: Tchounwou
authors.forename: Christian
authors.initials: C
authors.lastname: Rogers
mesh_terms: D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020552:Comet Assay; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects*; D019073:HT29 Cells; D006801:Humans; D009153:Mutagens / Q000494:pharmacology*; D010087:Oxides / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
chemical_list: D001152:Arsenicals; D009153:Mutagens; D010087:Oxides; D000077237:Arsenic Trioxide; D013936:Thymidine