title: Cadmium Chloride Induces DNA Damage and Apoptosis of Human Liver Carcinoma Cells via Oxidative Stress.
abstract: Cadmium is a heavy metal that has been shown to cause its toxicity in humans and animals. Many documented studies have shown that cadmium produces various genotoxic effects such as DNA damage and chromosomal aberrations. Ailments such as bone disease, renal damage, and several forms of cancer are attributed to overexposure to cadmium. Although there have been numerous studies examining the effects of cadmium in animal models and a few case studies involving communities where cadmium contamination has occurred, its molecular mechanisms of action are not fully elucidated. In this research, we hypothesized that oxidative stress plays a key role in cadmium chloride-induced toxicity, DNA damage, and apoptosis of human liver carcinoma (HepG₂) cells. To test our hypothesis, cell viability was determined by MTT assay. Lipid hydroperoxide content stress was estimated by lipid peroxidation assay. Genotoxic damage was tested by the means of alkaline single cell gel electrophoresis (Comet) assay. Cell apoptosis was measured by flow cytometry assessment (Annexin-V/PI assay). The result of MTT assay indicated that cadmium chloride induces toxicity to HepG₂ cells in a concentration-dependent manner, showing a 48 hr-LD50 of 3.6 µg/mL. Data generated from lipid peroxidation assay resulted in a significant (p < 0.05) increase of hydroperoxide production, specifically at the highest concentration tested. Data obtained from the Comet assay indicated that cadmium chloride causes DNA damage in HepG₂ cells in a concentration-dependent manner. A strong concentration-response relationship (p < 0.05) was recorded between annexin V positive cells and cadmium chloride exposure. In summary, these in vitro studies provide clear evidence that cadmium chloride induces oxidative stress, DNA damage, and programmed cell death in human liver carcinoma (HepG₂) cells.
authors.affiliation: Molecular Toxicology Research Laboratory, NIH-Center for Environmental Health, College of Science, Engineering and Technology, Jackson State University, 1400 Lynch Street, Box 18540, Jackson, MS 39217, USA. anthony.c.skipper@gmail.com.
authors.forename: Anthony
authors.initials: A
authors.lastname: Skipper
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Bookline Avenue, Boston, MA 02215, USA. jnsims@bidmc.harvard.edu.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Sims
authors.affiliation: Molecular Toxicology Research Laboratory, NIH-Center for Environmental Health, College of Science, Engineering and Technology, Jackson State University, 1400 Lynch Street, Box 18540, Jackson, MS 39217, USA. clement.yedjou@jsums.edu.
authors.forename: Clement G
authors.initials: CG
authors.lastname: Yedjou
authors.affiliation: Molecular Toxicology Research Laboratory, NIH-Center for Environmental Health, College of Science, Engineering and Technology, Jackson State University, 1400 Lynch Street, Box 18540, Jackson, MS 39217, USA. paul.b.tchounwou@jsums.edu.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Tchounwou
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D019256:Cadmium Chloride / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects*; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D056945:Hep G2 Cells; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D004785:Environmental Pollutants; D019256:Cadmium Chloride
keywords: DNA damage; HepG2 cells; apoptosis; cadmium chloride; cytotoxicity; oxidative stress