Thresholds for indirect DNA damage across cellular barriers for orthopaedic biomaterials.
Cobalt-chromium particles and ions can induce indirect DNA damage and chromosome aberrations in human cells on the other side of a cellular barrier in tissue culture. This occurs by intercellular signalling across the barrier. We now show that the threshold for this effect depends on the metal form and the particle composition. Ionic cobalt and chromium induced single strand breaks at concentrations equivalent to those found in the blood of patients with well functioning metal on metal hip prostheses. However, they only caused double strand breaks if the chromium was present as chromium (VI), and did not induce chromosome aberrations. Nanoparticles of cobalt-chromium alloy caused DNA double strand breaks and chromosome aberrations, of which the majority were tetraploidy. Ceramic nanoparticles induced only single strand breaks and/or alkaline labile sites when indirectly exposed to human fibroblasts. The assessment of reproductive risk from maternal exposure to biomaterials is not yet possible with epidemiology. Whilst the barrier model used here differs from the in vivo situation in several respects, it may be useful as a framework to evaluate biomaterial induced damage across physiological barriers.
Bristol Implant Research Centre, Department of Clinical Sciences at North Bristol, Bristol, UK.
Michael C
MC
Parry
Gevdeep
G
Bhabra
Aman
A
Sood
Filipa
F
Machado
Laura
L
Cartwright
Margaret
M
Saunders
E
E
Ingham
R
R
Newson
Ashley W
AW
Blom
Charles P
CP
Case
D000497:Alloys / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D019644:Arthroplasty, Replacement, Hip; D001672:Biocompatible Materials / Q000494:pharmacology*; D002478:Cells, Cultured; D002516:Ceramics / Q000737:chemistry / Q000494:pharmacology; D002857:Chromium / Q000737:chemistry / Q000494:pharmacology*; D002869:Chromosome Aberrations / Q000139:chemically induced; D003035:Cobalt / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007621:Karyotyping; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000737:chemistry; D009985:Orthopedics; D010920:Placenta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy
D000497:Alloys; D001672:Biocompatible Materials; D002857:Chromium; D003035:Cobalt; D004247:DNA