title: Lead-Induced Cell Cycle Arrest in Human Liver Carcinoma (HepG2) Cells: Involvement of oxidative stress, p53 andCyclinA.
abstract: BACKGROUND
  Recent studies in our laboratory have demonstrated that lead is cytotoxic to human liver carcinoma (HepG2) cells, showing a 48 h-LD50of 35.5 ± 9.2ug/mL. However, its molecular mechanisms of toxicity are still largely unknown. Hence, the aim of the present study was to use HepG2cells as a test model to investigate the molecular mechanisms of lead-induced oxidative stress and modulation of cellular response proteins.
  
  
  METHODS
  To achieve this goal, we performed lipid peroxidation assay for malondialdehyde (MDA) determination, western blot and densitometric analyses for genes and related proteins expression in human liver carcinoma cells.
  
  
  RESULTS
  Data obtained from the lipid peroxidation assay demonstrated a significant increase (p ≤ 0.05) of MDA levels in lead-treated HepG2cells compared to control cells. Western Blot analysis showed a strong dose-response relationship with regard to p53 expression, and a significant repression incyclin Ain lead-treated cells.
  
  
  CONCLUSIONS
  Findings from this research indicate that lead is able to cause oxidative stress, cell cycle arrest through activation of the 53-kDa tumor suppressor protein and down regulation of thecyclinA protein in human liver carcinoma (HepG2) cells.
authors.affiliation: Cellomics and Toxicogenomics Research Laboratory, NIH-Center for Environmental Health, College of Science, Engineering and Technology, Jackson State University, 1400 Lynch Street, P.O. Box 18540, Jackson, Mississippi, USA.
authors.forename: Clement G
authors.initials: CG
authors.lastname: Yedjou
authors.affiliation: Cellomics and Toxicogenomics Research Laboratory, NIH-Center for Environmental Health, College of Science, Engineering and Technology, Jackson State University, 1400 Lynch Street, P.O. Box 18540, Jackson, Mississippi, USA.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Tchounwou
keywords: HepG2 cells; Lead; cyclin A; lipid peroxidation; p53