title: Reactive oxygen species mediate Cr(VI)-induced S phase arrest through p53 in human colon cancer cells.
abstract: Compounds that contain chromate (Cr(VI)) are well-known carcinogens that are present in both industrial settings and the environment. The mechanism of carcinogenesis associated with these compounds is not well understood. This study focused on Cr(VI)-induced cell cycle arrest in human colon adenocarcinoma DLD1 cells. Treatment of the cells with Cr(VI) at 2.5 µM caused a growth arrest at the S phase. An increase in Cr(VI) concentration enhanced the growth arrest. Superoxide dismutase did not alter the Cr(VI)-induced S phase arrest. Catalase inhibited S-cell growth, indicating that H(2)O(2) is an important mediator in Cr(VI)-induced S phase arrest. Electron spin resonance spin-trapping measurements showed that incubation of cells with Cr(VI) generated hydroxyl radical (·OH). Catalase inhibited ·OH generation, indicating that H(2)O(2) was generated from cells stimulated by Cr(VI) and that H(2)O(2) functioned as a precursor of ·OH radical generation. p53, an oxidative response transcription factor, was activated upon Cr(VI) stimulation. Inhibition of p53 by introducing small hairpin RNA decreased S phase arrest induced by Cr(VI). These results support the following conclusions: (1) reactive oxygen species (ROS) are generated in Cr(VI)-stimulated DLD1 cells; (2) among the ROS generated, H(2)O(2) played a major role in causing S phase arrest in DLD1 cells; and (3) ROS mediated S phase arrest through a p53-dependent pathway.
authors.affiliation: Graduate Center for Toxicology, University of Kentucky, Lexington, USA.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Sun
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Yao
authors.forename: Wenqi
authors.initials: W
authors.lastname: Li
authors.forename: Young-Ok
authors.initials: YO
authors.lastname: Son
authors.forename: Jia
authors.initials: J
authors.lastname: Luo
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D002374:Catalase / Q000494:pharmacology; D045744:Cell Line, Tumor; D002840:Chromates / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006878:Hydroxides / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016196:S Phase / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002840:Chromates; D006878:Hydroxides; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C031356:hydroxide ion; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase