Lead-Induced Cell Cycle Arrest in Human Liver Carcinoma (HepG2) Cells: Involvement of oxidative stress, p53 and Cyclin A.

Abstract

Background: Recent studies in our laboratory have demonstrated that lead is cytotoxic to human liver carcinoma (HepG₂) cells, showing a 48 h-LD₅₀ of 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 HepG₂ cells 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 HepG₂ cells compared to control cells. Western Blot analysis showed a strong dose-response relationship with regard to p53 expression, and a significant repression in cyclin A in 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 the cyclin A protein in human liver carcinoma (HepG₂) cells.