title: N-Acetyl-cysteine Protection Against Lead-Induced Oxidative Stress and Genotoxicity in Human Liver Carcinoma (HepG2) Cells.
abstract: The human liver carcinoma (HepG2) cells as well as other cell lines are particularly susceptible to oxidative damage, and it is therefore important to find agents that protect against this process. N-acetyl-cysteine (NAC) is the acetylated form of L-cysteine. It has an impressive list of protective effects including: antioxidant activity, decrease of the biologically effective dose of carcinogens, anti-inflammatory activity, immunological effects, inhibition of progression to malignancy and metastasis, and protection from the adverse effects of chemopreventive and chemotherapeutic agents. Previous studies in our laboratory have shown that lead nitrate induces cytotoxicity and oxidative stress to HepG2cells in a dose-dependent manner. In this research, we hypothesized that the antioxidant, n-acetyl-l-cysteine attenuates oxidative stress and genotoxicity, and thereby provides cellular protection against lead toxicity. To this hypothesis, we performed the thiobarbituric acid test for lipid peroxidation and the microgel electrophoresis (comet) assay for genotoxicity. The results generated from the thiobarbituric acid test showed a significant reduction of lipid peroxidation by-product (malondialdehyde) in HepG2cells co-exposed to NAC and lead nitrate compared to lead nitrate alone. Incubation of HepG2cells with increasing concentrations of NAC decreased the amount of MDA formation progressively in lead nitrate-treated HepG2cells. Data obtained from the comet assay indicated a strong dose-response relationship with regard to lead nitrate-induced genotoxic damage in HepG2cells. However, the addition of NACin vitroshowed a significant reduction (p < 0.05) in the comet tail length, percentage of DNA cleavage, comet tail moment, as well as comet tail arm respectively in cells co-treated with NAC and lead nitrate. Findings from these studies demonstrated that NAC inhibits malondialdehyde (MDA) production and genotoxicity in lead nitrate-treated HepG2cells in a dose-dependent manner. Under thisin vitrocondition, NAC was found to be effective in reducing MDA formation, cellular injury, and genotoxic damage in HepG2cells exposed to lead nitrate.
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: Daren
authors.initials: D
authors.lastname: Waters
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