N-acetyl-cysteine protects against DNA damage associated with lead toxicity in HepG2 cells.
Lead toxicity has been associated with its ability to interact and damage DNA. However, its molecular mechanisms of action are not fully understood. In vitro studies in our laboratory indicated that lead nitrate (PbNO3) induces cytotoxicity and oxidative stress to human liver carcinoma (HepG2) cells in a dose-dependent manner. In this research, we hypothesized that n-acetyl-cysteine (NAC), a known antioxidant compound, affords protection against lead-induced cell death associated with genotoxic damage. To test this hypothesis, HepG2 cells were treated either with a physiologic dose of NAC, NAC plus PbNO3, or PbNO3 alone, followed by incubation in humidified 5% CO2 incubator at 37 degrees C for 48 hr. The cell viability was determined by trypan blue exclusion test. The degree of DNA damage was detected by micro gel electrophoresis (comet) assay. Our results showed that lead exposure induces a substantial cytotoxicity as well as a significant genotoxicity to HepG2 cells. However, co-treatment with a physiologic dose (500 microM) of NAC slightly increases cell viability, and significantly reduced (P < .05) the degree of DNA damage. Hence, NAC treatment may be a promising therapeutic candidate for chemoprevention against lead toxicity, based on its ability to scavenge free radicals.
Cellomics and Toxicogenomics Research Laboratory, RCMI-Center for Environmental Health, College of Science, Engineering and Technology, Jackson State University, Jackson, Mississippi 39217-0002, USA. clement.yedjou@jsums.edu
Clement G
CG
Yedjou
Christine K
CK
Tchounwou
Samuel
S
Haile
Falicia
F
Edwards
Paul B
PB
Tchounwou
D000111:Acetylcysteine / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D007854:Lead / Q000633:toxicity*; D008113:Liver Neoplasms / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects
D016166:Free Radical Scavengers; D007854:Lead; D000111:Acetylcysteine