Reactive oxygen species mediate Cr(VI)-induced S phase arrest through p53 in human colon cancer cells

Lijuan Sun, Xin Wang, Hua Yao, Wenqi Li, Young Ok Son, Jia Luo, Jiankang Liu, Zhuo Zhang

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 H2 O2 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 H2 O2 was generated from cells stimulated by Cr(VI) and that H2 O2 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, H2 O2 played a major role in causing S phase arrest in DLD1 cells; and (3) ROS mediated S phase arrest through a p53-dependent pathway.

Original languageEnglish
Pages (from-to)95-107
Number of pages13
JournalJournal of Environmental Pathology, Toxicology and Oncology
Volume31
Issue number2
DOIs
StatePublished - 2012

Keywords

  • Cell cycle
  • Cell cycle checkpoints
  • Chromium (VI)
  • Human colon cancer
  • Reactive oxygen species
  • p53

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Toxicology
  • Health, Toxicology and Mutagenesis

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