The Cytotoxicity and Genotoxicity of Particulate and Soluble Cobalt in Human Urothelial Cells.
Cobalt use is increasing particularly due to its use as one of the primary metals in cobalt-chromium-molybdenum (CoCrMo) metal-on-metal prosthetics. CoCrMo is a high-strength, wear-resistant alloy with reduced risk for prosthetic loosening and device fracture. More than 500,000 people receive hip implants each year in the USA which puts them at potential risk for exposure to metal ions and particles released by the prosthetic implants. Data show cobalt ions released from prosthetics reach the bloodstream and accumulate in the bladder. As patients with failed hip implants show increased urinary and blood cobalt levels, no studies have considered the effects of cobalt on human urothelial cells. Accordingly, we investigated the cytotoxic and genotoxic effects of particulate and soluble cobalt in urothelial cells. Exposure to both particulate and soluble cobalt resulted in a concentration-dependent increase in cytotoxicity, genotoxicity, and intracellular cobalt ions. Based on intracellular cobalt ion levels, we found, when compared to particulate cobalt, soluble cobalt was more cytotoxic, but induced similar levels of genotoxicity. Interestingly, at similar intracellular cobalt ion concentrations, soluble cobalt induced cell cycle arrest indicated by a lack of metaphases not observed after particulate cobalt treatment. These data indicate that cobalt compounds are cytotoxic and genotoxic to human urothelial cells and solubility may play a key role in cobalt-induced toxicity.
Wise Laboratory of Environmental and Genetic Toxicology, University of Louisville, 505 S. Hancock St, CTRB rm 522, Louisville, KY, 40292, USA.
Rachel M
RM
Speer
Wise Laboratory of Environmental and Genetic Toxicology, University of Louisville, 505 S. Hancock St, CTRB rm 522, Louisville, KY, 40292, USA.|Maine General Health, Alfonso Center of Health, Histology and Cytology Laboratory, 35 Medical Center Parkway, Augusta, ME, 04330, USA.
Therry
T
The
Wise Laboratory of Environmental and Genetic Toxicology, University of Louisville, 505 S. Hancock St, CTRB rm 522, Louisville, KY, 40292, USA.|Toxikon Corp, 15 Wiggins Avenue, Bedford, MA, 01730, USA.
Hong
H
Xie
Cambridge Health Alliance Somerville Hospital, 230 Highland Avenue, 4th Floor South Building, Somerville, MA, 02143, USA.
Louis
L
Liou
Department of Urology, Enders Research Building, Rm 1061.1, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
Rosalyn M
RM
Adam
Wise Laboratory of Environmental and Genetic Toxicology, University of Louisville, 505 S. Hancock St, CTRB rm 522, Louisville, KY, 40292, USA. jpwise07@louisville.edu.
John Pierce
JP
Wise
D002460:Cell Line; D003035:Cobalt / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006622:Hip Prosthesis; D006801:Humans; D009152:Mutagenicity Tests; D012995:Solubility; D018675:Toxicity Tests; D019459:Urothelium / Q000166:cytology*
D003035:Cobalt
Cobalt; Cobalt chloride; Cobalt oxide; Cytotoxicity; Genotoxicity