Signalling of DNA damage and cytokines across cell barriers exposed to nanoparticles depends on barrier thickness

A. Sood; S. Salih; D. Roh; L. Lacharme-Lora; M. Parry; B. Hardiman; R. Keehan; R. Grummer; E. Winterhager; P. J. Gokhale; P. W. Andrews; C. Abbott; K. Forbes; M. Westwood; J. D. Aplin; E. Ingham; I. Papageorgiou; M. Berry; J. Liu; A. D. Dick; R. J. Garland; N. Williams; R. Singh; A. K. Simon; M. Lewis; J. Ham; L. Roger; D. M. Baird; L. A. Crompton; M. A. Caldwell; H. Swalwell; M. Birch-Machin; G. Lopez-Castejon; A. Randall; H. Lin; M. S. Suleiman; W. H. Evans; R. Newson; C. P. Case

doi:10.1038/nnano.2011.188

Signalling of DNA damage and cytokines across cell barriers exposed to nanoparticles depends on barrier thickness

A. Sood, S. Salih, D. Roh, L. Lacharme-Lora, M. Parry, B. Hardiman, R. Keehan, R. Grummer, E. Winterhager, P. J. Gokhale, P. W. Andrews, C. Abbott, K. Forbes, M. Westwood, J. D. Aplin, E. Ingham, I. Papageorgiou, M. Berry, J. Liu, A. D. DickR. J. Garland, N. Williams, R. Singh, A. K. Simon, M. Lewis, J. Ham, L. Roger, D. M. Baird, L. A. Crompton, M. A. Caldwell, H. Swalwell, M. Birch-Machin, G. Lopez-Castejon, A. Randall, H. Lin, M. S. Suleiman, W. H. Evans, R. Newson, C. P. Case

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Abstract

The use of nanoparticles in medicine is ever increasing, and it is important to understand their targeted and non-targeted effects. We have previously shown that nanoparticles can cause DNA damage to cells cultured below a cellular barrier without crossing this barrier. Here, we show that this indirect DNA damage depends on the thickness of the cellular barrier, and it is mediated by signalling through gap junction proteins following the generation of mitochondrial free radicals. Indirect damage was seen across both trophoblast and corneal barriers. Signalling, including cytokine release, occurred only across bilayer and multilayer barriers, but not across monolayer barriers. Indirect toxicity was also observed in mice and using ex vivo explants of the human placenta. If the importance of barrier thickness in signalling is a general feature for all types of barriers, our results may offer a principle with which to limit the adverse effects of nanoparticle exposure and offer new therapeutic approaches. © 2011 Macmillan Publishers Limited. All rights reserved.

Original language	English
Pages (from-to)	824-833
Number of pages	9
Journal	Nature Nanotechnology
Volume	6
Issue number	12
DOIs	https://doi.org/10.1038/nnano.2011.188
Publication status	Published - Dec 2011

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10.1038/nnano.2011.188

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Sood, A., Salih, S., Roh, D., Lacharme-Lora, L., Parry, M., Hardiman, B., Keehan, R., Grummer, R., Winterhager, E., Gokhale, P. J., Andrews, P. W., Abbott, C., Forbes, K., Westwood, M., Aplin, J. D., Ingham, E., Papageorgiou, I., Berry, M., Liu, J., ... Case, C. P. (2011). Signalling of DNA damage and cytokines across cell barriers exposed to nanoparticles depends on barrier thickness. Nature Nanotechnology, 6(12), 824-833. https://doi.org/10.1038/nnano.2011.188

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title = "Signalling of DNA damage and cytokines across cell barriers exposed to nanoparticles depends on barrier thickness",

abstract = "The use of nanoparticles in medicine is ever increasing, and it is important to understand their targeted and non-targeted effects. We have previously shown that nanoparticles can cause DNA damage to cells cultured below a cellular barrier without crossing this barrier. Here, we show that this indirect DNA damage depends on the thickness of the cellular barrier, and it is mediated by signalling through gap junction proteins following the generation of mitochondrial free radicals. Indirect damage was seen across both trophoblast and corneal barriers. Signalling, including cytokine release, occurred only across bilayer and multilayer barriers, but not across monolayer barriers. Indirect toxicity was also observed in mice and using ex vivo explants of the human placenta. If the importance of barrier thickness in signalling is a general feature for all types of barriers, our results may offer a principle with which to limit the adverse effects of nanoparticle exposure and offer new therapeutic approaches. {\textcopyright} 2011 Macmillan Publishers Limited. All rights reserved.",

author = "A. Sood and S. Salih and D. Roh and L. Lacharme-Lora and M. Parry and B. Hardiman and R. Keehan and R. Grummer and E. Winterhager and Gokhale, {P. J.} and Andrews, {P. W.} and C. Abbott and K. Forbes and M. Westwood and Aplin, {J. D.} and E. Ingham and I. Papageorgiou and M. Berry and J. Liu and Dick, {A. D.} and Garland, {R. J.} and N. Williams and R. Singh and Simon, {A. K.} and M. Lewis and J. Ham and L. Roger and Baird, {D. M.} and Crompton, {L. A.} and Caldwell, {M. A.} and H. Swalwell and M. Birch-Machin and G. Lopez-Castejon and A. Randall and H. Lin and Suleiman, {M. S.} and Evans, {W. H.} and R. Newson and Case, {C. P.}",

year = "2011",

month = dec,

doi = "10.1038/nnano.2011.188",

language = "English",

volume = "6",

pages = "824--833",

journal = "Nature Nanotechnology",

issn = "1748-3387",

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Sood, A, Salih, S, Roh, D, Lacharme-Lora, L, Parry, M, Hardiman, B, Keehan, R, Grummer, R, Winterhager, E, Gokhale, PJ, Andrews, PW, Abbott, C, Forbes, K, Westwood, M , Aplin, JD, Ingham, E, Papageorgiou, I, Berry, M, Liu, J, Dick, AD, Garland, RJ, Williams, N, Singh, R, Simon, AK, Lewis, M, Ham, J, Roger, L, Baird, DM, Crompton, LA, Caldwell, MA, Swalwell, H, Birch-Machin, M, Lopez-Castejon, G, Randall, A, Lin, H, Suleiman, MS, Evans, WH, Newson, R & Case, CP 2011, 'Signalling of DNA damage and cytokines across cell barriers exposed to nanoparticles depends on barrier thickness', Nature Nanotechnology, vol. 6, no. 12, pp. 824-833. https://doi.org/10.1038/nnano.2011.188

TY - JOUR

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AU - Sood, A.

AU - Salih, S.

AU - Roh, D.

AU - Lacharme-Lora, L.

AU - Parry, M.

AU - Hardiman, B.

AU - Keehan, R.

AU - Grummer, R.

AU - Winterhager, E.

AU - Gokhale, P. J.

AU - Andrews, P. W.

AU - Abbott, C.

AU - Forbes, K.

AU - Westwood, M.

AU - Aplin, J. D.

AU - Ingham, E.

AU - Papageorgiou, I.

AU - Berry, M.

AU - Liu, J.

AU - Dick, A. D.

AU - Garland, R. J.

AU - Williams, N.

AU - Singh, R.

AU - Simon, A. K.

AU - Lewis, M.

AU - Ham, J.

AU - Roger, L.

AU - Baird, D. M.

AU - Crompton, L. A.

AU - Caldwell, M. A.

AU - Swalwell, H.

AU - Birch-Machin, M.

AU - Lopez-Castejon, G.

AU - Randall, A.

AU - Lin, H.

AU - Suleiman, M. S.

AU - Evans, W. H.

AU - Newson, R.

AU - Case, C. P.

PY - 2011/12

Y1 - 2011/12

N2 - The use of nanoparticles in medicine is ever increasing, and it is important to understand their targeted and non-targeted effects. We have previously shown that nanoparticles can cause DNA damage to cells cultured below a cellular barrier without crossing this barrier. Here, we show that this indirect DNA damage depends on the thickness of the cellular barrier, and it is mediated by signalling through gap junction proteins following the generation of mitochondrial free radicals. Indirect damage was seen across both trophoblast and corneal barriers. Signalling, including cytokine release, occurred only across bilayer and multilayer barriers, but not across monolayer barriers. Indirect toxicity was also observed in mice and using ex vivo explants of the human placenta. If the importance of barrier thickness in signalling is a general feature for all types of barriers, our results may offer a principle with which to limit the adverse effects of nanoparticle exposure and offer new therapeutic approaches. © 2011 Macmillan Publishers Limited. All rights reserved.

AB - The use of nanoparticles in medicine is ever increasing, and it is important to understand their targeted and non-targeted effects. We have previously shown that nanoparticles can cause DNA damage to cells cultured below a cellular barrier without crossing this barrier. Here, we show that this indirect DNA damage depends on the thickness of the cellular barrier, and it is mediated by signalling through gap junction proteins following the generation of mitochondrial free radicals. Indirect damage was seen across both trophoblast and corneal barriers. Signalling, including cytokine release, occurred only across bilayer and multilayer barriers, but not across monolayer barriers. Indirect toxicity was also observed in mice and using ex vivo explants of the human placenta. If the importance of barrier thickness in signalling is a general feature for all types of barriers, our results may offer a principle with which to limit the adverse effects of nanoparticle exposure and offer new therapeutic approaches. © 2011 Macmillan Publishers Limited. All rights reserved.

U2 - 10.1038/nnano.2011.188

DO - 10.1038/nnano.2011.188

M3 - Article

C2 - 22056725

SN - 1748-3387

VL - 6

SP - 824

EP - 833

JO - Nature Nanotechnology

JF - Nature Nanotechnology

IS - 12

ER -

Signalling of DNA damage and cytokines across cell barriers exposed to nanoparticles depends on barrier thickness

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