Investigating cobalt toxicity in the context of joint replacement patients - cobalt uptake in primary cardiac fibroblasts and in 3T3 cells

Sarunya Laovitthayanggoon, M. Helen Grant, Catherine J. Henderson, Rothwelle J. Tate, Susan Currie

Research output: Contribution to journalMeeting abstract

Abstract

Cobalt leaches out from cobalt/chromium metal-on-metal hip implants into patient blood, and its effects are thought to be toxic. There has been a 5% estimated incidence of adverse effects, including toxicity to the heart, in joint implant patients over the last 40 years. This was investigated by examination of the effects of CoCl2 on cell proliferation and viability performed using a range of assays. To assess effects on proliferation, MTT, neutral red and crystal violet assays were all used to compare effects of increasing concentrations of CoCl2 on the Swiss 3T3 fibroblast cell line (3T3s) and primary cardiac fibroblasts (CFs). CoCl2 induced toxicity in both 3T3s and CFs in a time- and dose-dependent manner with IC50 values for CoCl2 in the range of ~300 µM in both cells. Over 72h, increasing CoCl2 concentrations (up to 500 µM) resulted in decreased proliferation. Interestingly, in terms of proliferation, the 3T3s were more tolerant of CoCl2 than CFs. Uptake of CoCl2 into the 3T3s and CFs was measured by detecting intracellular metal content using ICP-MS. Cells were cultured and exposed to various concentrations of CoCl2 (0-72 ppm) and different exposure times (24, 48 and 72 h). Analysis of cobalt content of cells revealed that with increasing medium concentration of CoCl2 intracellular Co concentration on both 3T3s and CFs increased, to a range between 0-50 ppb and 0-120 ppb, respectively. Uptake into CFs was greater than into the 3T3s, and this at least partly explains the difference in toxicity between the two cell types.

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Replacement Arthroplasties
3T3 Cells
Fibroblasts
Cobalt
Toxicity
Metals
Assays
Swiss 3T3 Cells
Gentian Violet
Neutral Red
Poisons
Cell proliferation
Chromium
Inhibitory Concentration 50
Hip
Cultured Cells
Cell Survival
Blood
Joints
Cells

Keywords

  • cobalt toxicity
  • joint replacement patients
  • primary cardiac fibroblasts
  • 3T3 cells

Cite this

@article{d80598a84ff84d5d932577052569b984,
title = "Investigating cobalt toxicity in the context of joint replacement patients - cobalt uptake in primary cardiac fibroblasts and in 3T3 cells",
abstract = "Cobalt leaches out from cobalt/chromium metal-on-metal hip implants into patient blood, and its effects are thought to be toxic. There has been a 5{\%} estimated incidence of adverse effects, including toxicity to the heart, in joint implant patients over the last 40 years. This was investigated by examination of the effects of CoCl2 on cell proliferation and viability performed using a range of assays. To assess effects on proliferation, MTT, neutral red and crystal violet assays were all used to compare effects of increasing concentrations of CoCl2 on the Swiss 3T3 fibroblast cell line (3T3s) and primary cardiac fibroblasts (CFs). CoCl2 induced toxicity in both 3T3s and CFs in a time- and dose-dependent manner with IC50 values for CoCl2 in the range of ~300 µM in both cells. Over 72h, increasing CoCl2 concentrations (up to 500 µM) resulted in decreased proliferation. Interestingly, in terms of proliferation, the 3T3s were more tolerant of CoCl2 than CFs. Uptake of CoCl2 into the 3T3s and CFs was measured by detecting intracellular metal content using ICP-MS. Cells were cultured and exposed to various concentrations of CoCl2 (0-72 ppm) and different exposure times (24, 48 and 72 h). Analysis of cobalt content of cells revealed that with increasing medium concentration of CoCl2 intracellular Co concentration on both 3T3s and CFs increased, to a range between 0-50 ppb and 0-120 ppb, respectively. Uptake into CFs was greater than into the 3T3s, and this at least partly explains the difference in toxicity between the two cell types.",
keywords = "cobalt toxicity, joint replacement patients, primary cardiac fibroblasts, 3T3 cells",
author = "Sarunya Laovitthayanggoon and Grant, {M. Helen} and Henderson, {Catherine J.} and Tate, {Rothwelle J.} and Susan Currie",
year = "2016",
month = "12",
day = "1",
doi = "10.1089/aivt.2016.29007.abstracts",
language = "English",
volume = "2",
journal = "Applied in Vitro Toxicology",
issn = "2332-1512",
publisher = "Mary Ann Liebert Inc.",
number = "4",

}

TY - JOUR

T1 - Investigating cobalt toxicity in the context of joint replacement patients - cobalt uptake in primary cardiac fibroblasts and in 3T3 cells

AU - Laovitthayanggoon, Sarunya

AU - Grant, M. Helen

AU - Henderson, Catherine J.

AU - Tate, Rothwelle J.

AU - Currie, Susan

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Cobalt leaches out from cobalt/chromium metal-on-metal hip implants into patient blood, and its effects are thought to be toxic. There has been a 5% estimated incidence of adverse effects, including toxicity to the heart, in joint implant patients over the last 40 years. This was investigated by examination of the effects of CoCl2 on cell proliferation and viability performed using a range of assays. To assess effects on proliferation, MTT, neutral red and crystal violet assays were all used to compare effects of increasing concentrations of CoCl2 on the Swiss 3T3 fibroblast cell line (3T3s) and primary cardiac fibroblasts (CFs). CoCl2 induced toxicity in both 3T3s and CFs in a time- and dose-dependent manner with IC50 values for CoCl2 in the range of ~300 µM in both cells. Over 72h, increasing CoCl2 concentrations (up to 500 µM) resulted in decreased proliferation. Interestingly, in terms of proliferation, the 3T3s were more tolerant of CoCl2 than CFs. Uptake of CoCl2 into the 3T3s and CFs was measured by detecting intracellular metal content using ICP-MS. Cells were cultured and exposed to various concentrations of CoCl2 (0-72 ppm) and different exposure times (24, 48 and 72 h). Analysis of cobalt content of cells revealed that with increasing medium concentration of CoCl2 intracellular Co concentration on both 3T3s and CFs increased, to a range between 0-50 ppb and 0-120 ppb, respectively. Uptake into CFs was greater than into the 3T3s, and this at least partly explains the difference in toxicity between the two cell types.

AB - Cobalt leaches out from cobalt/chromium metal-on-metal hip implants into patient blood, and its effects are thought to be toxic. There has been a 5% estimated incidence of adverse effects, including toxicity to the heart, in joint implant patients over the last 40 years. This was investigated by examination of the effects of CoCl2 on cell proliferation and viability performed using a range of assays. To assess effects on proliferation, MTT, neutral red and crystal violet assays were all used to compare effects of increasing concentrations of CoCl2 on the Swiss 3T3 fibroblast cell line (3T3s) and primary cardiac fibroblasts (CFs). CoCl2 induced toxicity in both 3T3s and CFs in a time- and dose-dependent manner with IC50 values for CoCl2 in the range of ~300 µM in both cells. Over 72h, increasing CoCl2 concentrations (up to 500 µM) resulted in decreased proliferation. Interestingly, in terms of proliferation, the 3T3s were more tolerant of CoCl2 than CFs. Uptake of CoCl2 into the 3T3s and CFs was measured by detecting intracellular metal content using ICP-MS. Cells were cultured and exposed to various concentrations of CoCl2 (0-72 ppm) and different exposure times (24, 48 and 72 h). Analysis of cobalt content of cells revealed that with increasing medium concentration of CoCl2 intracellular Co concentration on both 3T3s and CFs increased, to a range between 0-50 ppb and 0-120 ppb, respectively. Uptake into CFs was greater than into the 3T3s, and this at least partly explains the difference in toxicity between the two cell types.

KW - cobalt toxicity

KW - joint replacement patients

KW - primary cardiac fibroblasts

KW - 3T3 cells

UR - http://online.liebertpub.com/doi/pdfplus/10.1089/aivt.2016.29007.abstracts

U2 - 10.1089/aivt.2016.29007.abstracts

DO - 10.1089/aivt.2016.29007.abstracts

M3 - Meeting abstract

VL - 2

JO - Applied in Vitro Toxicology

T2 - Applied in Vitro Toxicology

JF - Applied in Vitro Toxicology

SN - 2332-1512

IS - 4

M1 - P-8

ER -