Study of TiO2 P25 nanoparticles genotoxicity on lung, blood and liver cells in lung overload and non-overload conditions after repeated respiratory exposure in rats

Charlène Relier, Marielle Dubreuil, Omar Lozano Garcia, Eugenia Cordelli, Jorge Humberto Mejia Mendoza, Patrizia Eleuteri, Franck Robidel, Thomas Loret, Francesca Pacchierotti, Stéphane Lucas, Ghislaine Lacroix, Bénédicte Trouiller

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

Inhaled titanium dioxide (TiO 2) nanoparticles (NPs) can have negative health effects, and have been shown to cause respiratory tract cancer in rats. Inflammation has been linked to oxidative stress, and both have been described as possible mechanisms for genotoxicity of NPs, but rarely examined side-by-side in animal studies. In the present study, a wide range of complementary endpoints have been performed to study TiO 2 P25NP-induced genotoxicity in lung overload and non-overload conditions. Additionally, lung burden, inflammation, cytotoxicity and oxidative stress have also been evaluated in order to link genotoxicity with these responses. To assess quick and delayed responses after recovery, endpoints were evaluated at two time points: 2 h and 35 days after three repeated instillations. This study confirmed the previously described lung overload threshold at approximately 200-300cm 2 of lung burden for total particle surface area lung deposition or 4.2 ml/kg for volume-based cumulative lung exposure dose, above which lung clearance is impaired and inflammation is induced. Our results went on to show that these overload doses induced delayed genotoxicity in lung, associated with persistent inflammation only at the highest dose. The lowest tested doses had no toxicity or genotoxicity effects in the lung. In blood, no lymphocyte DNA damage, erythrocytes chromosomal damage or gene mutation could be detected. Our data also demonstrated that only overload doses induced liver DNA lesions irrespective of the recovery time. Tested doses of TiO 2 P25 NPs did not induce glutathione changes in lung, blood or liver at both recovery times.

langue originaleAnglais
Numéro d'articlekfx006
Pages (de - à)527-537
Nombre de pages11
journalToxicological Sciences
Volume156
Numéro de publication2
Date de mise en ligne précoce13 janv. 2017
Les DOIs
étatPublié - 1 avr. 2017

Empreinte digitale

Liver
Nanoparticles
Rats
Blood Cells
Blood
Oxidative stress
Recovery
Lung
Lymphocytes
DNA
Cytotoxicity
Glutathione
Toxicity
Animals
Genes
Health
Inflammation
Oxidative Stress
Respiratory System
DNA Damage

Citer ceci

Relier, Charlène ; Dubreuil, Marielle ; Lozano Garcia, Omar ; Cordelli, Eugenia ; Mejia Mendoza, Jorge Humberto ; Eleuteri, Patrizia ; Robidel, Franck ; Loret, Thomas ; Pacchierotti, Francesca ; Lucas, Stéphane ; Lacroix, Ghislaine ; Trouiller, Bénédicte . / Study of TiO2 P25 nanoparticles genotoxicity on lung, blood and liver cells in lung overload and non-overload conditions after repeated respiratory exposure in rats. Dans: Toxicological Sciences. 2017 ; Vol 156, Numéro 2. p. 527-537.
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abstract = "Inhaled titanium dioxide (TiO 2) nanoparticles (NPs) can have negative health effects, and have been shown to cause respiratory tract cancer in rats. Inflammation has been linked to oxidative stress, and both have been described as possible mechanisms for genotoxicity of NPs, but rarely examined side-by-side in animal studies. In the present study, a wide range of complementary endpoints have been performed to study TiO 2 P25NP-induced genotoxicity in lung overload and non-overload conditions. Additionally, lung burden, inflammation, cytotoxicity and oxidative stress have also been evaluated in order to link genotoxicity with these responses. To assess quick and delayed responses after recovery, endpoints were evaluated at two time points: 2 h and 35 days after three repeated instillations. This study confirmed the previously described lung overload threshold at approximately 200-300cm 2 of lung burden for total particle surface area lung deposition or 4.2 ml/kg for volume-based cumulative lung exposure dose, above which lung clearance is impaired and inflammation is induced. Our results went on to show that these overload doses induced delayed genotoxicity in lung, associated with persistent inflammation only at the highest dose. The lowest tested doses had no toxicity or genotoxicity effects in the lung. In blood, no lymphocyte DNA damage, erythrocytes chromosomal damage or gene mutation could be detected. Our data also demonstrated that only overload doses induced liver DNA lesions irrespective of the recovery time. Tested doses of TiO 2 P25 NPs did not induce glutathione changes in lung, blood or liver at both recovery times.",
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Relier, C, Dubreuil, M, Lozano Garcia, O, Cordelli, E, Mejia Mendoza, JH, Eleuteri, P, Robidel, F, Loret, T, Pacchierotti, F, Lucas, S, Lacroix, G & Trouiller, B 2017, 'Study of TiO2 P25 nanoparticles genotoxicity on lung, blood and liver cells in lung overload and non-overload conditions after repeated respiratory exposure in rats', Toxicological Sciences, VOL. 156, Numéro 2, kfx006, p. 527-537. https://doi.org/10.1093/toxsci/kfx006

Study of TiO2 P25 nanoparticles genotoxicity on lung, blood and liver cells in lung overload and non-overload conditions after repeated respiratory exposure in rats. / Relier, Charlène ; Dubreuil, Marielle ; Lozano Garcia, Omar; Cordelli, Eugenia; Mejia Mendoza, Jorge Humberto; Eleuteri, Patrizia ; Robidel, Franck ; Loret, Thomas; Pacchierotti, Francesca ; Lucas, Stéphane; Lacroix, Ghislaine ; Trouiller, Bénédicte .

Dans: Toxicological Sciences, Vol 156, Numéro 2, kfx006, 01.04.2017, p. 527-537.

Résultats de recherche: Contribution à un journal/une revueArticle

TY - JOUR

T1 - Study of TiO2 P25 nanoparticles genotoxicity on lung, blood and liver cells in lung overload and non-overload conditions after repeated respiratory exposure in rats

AU - Relier, Charlène

AU - Dubreuil, Marielle

AU - Lozano Garcia, Omar

AU - Cordelli, Eugenia

AU - Mejia Mendoza, Jorge Humberto

AU - Eleuteri, Patrizia

AU - Robidel, Franck

AU - Loret, Thomas

AU - Pacchierotti, Francesca

AU - Lucas, Stéphane

AU - Lacroix, Ghislaine

AU - Trouiller, Bénédicte

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Inhaled titanium dioxide (TiO 2) nanoparticles (NPs) can have negative health effects, and have been shown to cause respiratory tract cancer in rats. Inflammation has been linked to oxidative stress, and both have been described as possible mechanisms for genotoxicity of NPs, but rarely examined side-by-side in animal studies. In the present study, a wide range of complementary endpoints have been performed to study TiO 2 P25NP-induced genotoxicity in lung overload and non-overload conditions. Additionally, lung burden, inflammation, cytotoxicity and oxidative stress have also been evaluated in order to link genotoxicity with these responses. To assess quick and delayed responses after recovery, endpoints were evaluated at two time points: 2 h and 35 days after three repeated instillations. This study confirmed the previously described lung overload threshold at approximately 200-300cm 2 of lung burden for total particle surface area lung deposition or 4.2 ml/kg for volume-based cumulative lung exposure dose, above which lung clearance is impaired and inflammation is induced. Our results went on to show that these overload doses induced delayed genotoxicity in lung, associated with persistent inflammation only at the highest dose. The lowest tested doses had no toxicity or genotoxicity effects in the lung. In blood, no lymphocyte DNA damage, erythrocytes chromosomal damage or gene mutation could be detected. Our data also demonstrated that only overload doses induced liver DNA lesions irrespective of the recovery time. Tested doses of TiO 2 P25 NPs did not induce glutathione changes in lung, blood or liver at both recovery times.

AB - Inhaled titanium dioxide (TiO 2) nanoparticles (NPs) can have negative health effects, and have been shown to cause respiratory tract cancer in rats. Inflammation has been linked to oxidative stress, and both have been described as possible mechanisms for genotoxicity of NPs, but rarely examined side-by-side in animal studies. In the present study, a wide range of complementary endpoints have been performed to study TiO 2 P25NP-induced genotoxicity in lung overload and non-overload conditions. Additionally, lung burden, inflammation, cytotoxicity and oxidative stress have also been evaluated in order to link genotoxicity with these responses. To assess quick and delayed responses after recovery, endpoints were evaluated at two time points: 2 h and 35 days after three repeated instillations. This study confirmed the previously described lung overload threshold at approximately 200-300cm 2 of lung burden for total particle surface area lung deposition or 4.2 ml/kg for volume-based cumulative lung exposure dose, above which lung clearance is impaired and inflammation is induced. Our results went on to show that these overload doses induced delayed genotoxicity in lung, associated with persistent inflammation only at the highest dose. The lowest tested doses had no toxicity or genotoxicity effects in the lung. In blood, no lymphocyte DNA damage, erythrocytes chromosomal damage or gene mutation could be detected. Our data also demonstrated that only overload doses induced liver DNA lesions irrespective of the recovery time. Tested doses of TiO 2 P25 NPs did not induce glutathione changes in lung, blood or liver at both recovery times.

KW - DNA damage

KW - Glutathione

KW - Inflammation

KW - Nanomaterials

KW - Rodents

KW - Titanium dioxide

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U2 - 10.1093/toxsci/kfx006

DO - 10.1093/toxsci/kfx006

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SP - 527

EP - 537

JO - Toxicological Sciences

JF - Toxicological Sciences

SN - 1096-6080

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