title: Cytotoxic, genotoxic, and neurotoxic effects of Mg, Pb, and Fe on pheochromocytoma (PC-12) cells.
abstract: Metals such as lead (Pb), magnesium (Mg), and iron (Fe) are ubiquitous in the environment as a result of natural occurrence and anthropogenic activities. Although Mg, Fe, and others are considered essential elements, high level of exposure has been associated with severe adverse health effects including cardiovascular, hematological, nephrotoxic, hepatotoxic, and neurologic abnormalities in humans. In the present study we hypothesized that Mg, Pb, and Fe are cytotoxic, genotoxic and neurotoxic, and their toxicity is mediated through oxidative stress and alteration in protein expression. To test the hypothesis, we used the pheochromocytoma (PC-12) cell line as a neuro cell model and performed the LDH assay for cell viability, Comet assay for DNA damage, Western blot for oxidative stress, and HPLC-MS to assess the concentration levels of neurological biomarkers such as glutamate, dopamine (DA), and 3-methoxytyramine (3-MT). The results of this study clearly show that Mg, Pb, and Fe, respectively in the form of MgSO4 , Pb(NO3 )2 , FeCl2 , and FeCl3 induce cytotoxicity, oxidative stress, and genotoxicity in PC-12 cells. In addition, exposure to these metallic compounds caused significant changes in the concentration levels of glutamate, dopamine, and 3-MT in PC-12 cells. Taken together the findings suggest that MgSO4 , Pb(NO3 )2 , FeCl2 , and FeCl3 have the potential to induce substantial toxicity to PC-12 cells.
authors.affiliation: Cellomics and Toxicogenomics Research Laboratory, NIH/NIMHD-RCMI Center for Environmental Health, Jackson State University, 1400 Lynch Street, Box18750, Jackson, Mississippi, 39217, USA.
authors.forename: Talia
authors.initials: T
authors.lastname: Sanders
authors.affiliation: Bioanalytical Research Laboratory, NIH/NIMHD-RCMI Center for Environmental Health, Jackson State University, 1400 Lynch Street, Box18750, Jackson, Mississippi, 39217, USA.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Liu
authors.affiliation: Cellomics and Toxicogenomics Research Laboratory, NIH/NIMHD-RCMI Center for Environmental Health, Jackson State University, 1400 Lynch Street, Box18750, Jackson, Mississippi, 39217, USA.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Tchounwou
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000633:toxicity*; D007854:Lead / Q000633:toxicity*; D008274:Magnesium / Q000633:toxicity*; D013058:Mass Spectrometry; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D010673:Pheochromocytoma / Q000378:metabolism / Q000473:pathology; D051381:Rats
chemical_list: D015415:Biomarkers; D018840:HSP70 Heat-Shock Proteins; D007854:Lead; D007501:Iron; D008274:Magnesium
keywords: PC-12 cells; cytotoxicity; genotoxicity; heavy metals; neurotoxicity