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Signalling of DNA damage and cytokines across cell barriers exposed to nanoparticles depends on barrier thickness
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Dr Helen Swalwell
Professor Mark Birch-Machin
Sood A, Salih S, Roh D, Lacharme-Lora L, Parry M, Hardiman B, Keehan R, Grummer R, Winterhager E, Andrews PW, Abbott C, Forbes K, Westwood M, Aplin JD, Ingham E, Papageoriou 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 MA, Lopez-Castejon G, Randall A, Lin H, Suleiman MS, Evans WH, Newson R, Case CP
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Nanoparticles are increasingly used in medicine and it is important to understand their targeted and non-targeted effects. Previously, we showed that nanoparticles can cause DNA damage to cells cultured below a cellular barrier without crossing the barrier. Here, we show that this indirect DNA damage caused by nanoparticles depends on the thickness of the cellular barrier and, is mediated by signalling through gap junction proteins between cells. Indirect damage was seen in both trophoblast and corneal barriers and, signalling occurred only in bilayered/multilayered, but not monolayered, barriers. Indirect toxicity was also observed in mice and in ex vivo cultures 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 way to limit the adverse effects of nanoparticle exposure and offer new therapeutic approaches.
Nature Publishing Group
Made a key material contribution to the successful acceptance of the paper i.e. designing and performing key experiments on mitochondrial DNA that the reveiwers requested in order for the paper to be accepted (have e-mail proof of this from correpsonding author Dr CASE in Bristol). I am the only contributor from Newcastle University and the only mitochondrial researcher.
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