The cytotoxicity and genotoxicity of soluble and particulate cobalt in human lung fibroblast cells.
Cobalt exposure is increasing as cobalt demand rises worldwide due to its use in enhancing rechargeable battery efficiency, super-alloys, and magnetic products. Cobalt is considered a possible human carcinogen with the lung being a primary target. However, few studies have considered cobalt-induced toxicity in human lung cells. Therefore, in this study, we sought to determine the cytotoxicity and genotoxicity of particulate and soluble cobalt in human lung cells. Cobalt oxide and cobalt chloride were used as representative particulate and soluble cobalt compounds, respectively. Exposure to both particulate and soluble cobalt induced a concentration-dependent increase in cytotoxicity, genotoxicity, and intracellular cobalt ion levels. Based on intracellular cobalt ion levels, we found that soluble cobalt was more cytotoxic than particulate cobalt while particulate and soluble cobalt induced similar levels of genotoxicity. However, soluble cobalt induced cell cycle arrest indicated by the lack of metaphases at much lower intracellular cobalt concentrations compared to cobalt oxide. Accordingly, we investigated the role of particle internalization in cobalt oxide-induced toxicity and found that particle-cell contact was necessary to induce cytotoxicity and genotoxicity after cobalt exposure. These data indicate that cobalt compounds are cytotoxic and genotoxic to human lung fibroblasts, and solubility plays a key role in cobalt-induced lung toxicity.
Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300, USA; Maine Center for Environmental Toxicology and Health, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300, USA; Department of Applied Medical Science, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300, USA.
Leah J
LJ
Smith
Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300, USA; Maine Center for Environmental Toxicology and Health, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300, USA; Department of Applied Medical Science, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300, USA.
Amie L
AL
Holmes
Department of Chemical & Biological Engineering, University of Maine, Orono, ME, USA.
Sanjeev Kumar
SK
Kandpal
Department of Chemical & Biological Engineering, University of Maine, Orono, ME, USA.
Michael D
MD
Mason
Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.
Tongzhang
T
Zheng
Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300, USA; Maine Center for Environmental Toxicology and Health, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300, USA; Department of Applied Medical Science, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300, USA. Electronic address: John.Wise@usm.maine.edu.
John Pierce
JP
Wise
D001692:Biological Transport; D002274:Carcinogens, Environmental / Q000032:analysis / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D002453:Cell Cycle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D003035:Cobalt / Q000032:analysis / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D009153:Mutagens / Q000032:analysis / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D009994:Osmolar Concentration; D010087:Oxides / Q000032:analysis / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects; D012995:Solubility
D002274:Carcinogens, Environmental; D009153:Mutagens; D010087:Oxides; D003035:Cobalt; C018021:cobaltous chloride; C060728:cobalt oxide
Cobalt; Cobalt chloride; Cobalt oxide; Cytotoxicity; Genotoxicity