Lysosomotropic-related limitations of the BALB/c 3T3 cell-based neutral red uptake assay and an alternative testing approach for assessing e-liquid cytotoxicity.
Identifieur interne : 000668 ( Main/Exploration ); précédent : 000667; suivant : 000669Lysosomotropic-related limitations of the BALB/c 3T3 cell-based neutral red uptake assay and an alternative testing approach for assessing e-liquid cytotoxicity.
Auteurs : Gianluca Cudazzo [Suisse] ; Daniel J. Smart [Suisse] ; Damian Mchugh [Suisse] ; Patrick Vanscheeuwijck [Suisse]Source :
- Toxicology in vitro : an international journal published in association with BIBRA [ 1879-3177 ] ; 2019.
Descripteurs français
- KwdFr :
- MESH :
- métabolisme : Lysosomes, Rouge neutre.
- toxicité : Nicotine.
- Animaux, Dosage biologique, Humains, Lignée cellulaire, Souris, Survie cellulaire.
English descriptors
- KwdEn :
- MESH :
- chemical , metabolism : Neutral Red.
- drug effects : Cell Survival.
- metabolism : Lysosomes.
- chemical , toxicity : Nicotine.
- Animals, Biological Assay, Cell Line, Electronic Nicotine Delivery Systems, Humans, Mice.
Abstract
Cytotoxicity assays are used to quantify the cytotoxic potential of chemicals. The neutral red uptake (NRU) assay is one of these assays and is routinely used in the pharmaceutical, cosmetic, and tobacco industries. In the context of e-cigarette development, an NRU assay-based screen was implemented to evaluate the cytotoxic potential of e-liquids. E-liquids induced a biphasic response in the BALB/c 3T3-based assay. The NRU initially increased in a concentration-dependent manner before decreasing following treatment with higher concentrations until NRU was abolished. Experiments were performed to characterize the mechanism underlying this biphasic signal. Nicotine alone was found to induce the same biphasic effects, while inducing concentration-dependent decreases in relative cell counts (RCC). Imaging and flow cytometry data revealed that the increases in NRU likely resulted from nicotine-induced vacuolization via a lysosomotropic mechanism. In support of this, two lysosomotropic agents, chloroquine and lapatinib, induced similar profiles. Nicotine's effects were also translatable, as brain-, lung-, bone marrow-, and smooth muscle-derived mammalian cells responded with the biphasic NRU signal. However, like RCC, three other cytotoxicity endpoints, resazurin, adenosine triphosphate, and water soluble tetrazolium salt (WST)-8, were not subject to these effects. The WST-8 assay is proposed as an alternative to screen the cytotoxic potential of e-liquids.
DOI: 10.1016/j.tiv.2019.104647
PubMed: 31518669
Affiliations:
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Le document en format XML
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Electronic address: damian.mchugh@pmi.com.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel</wicri:regionArea><wicri:noRegion>CH-2000 Neuchâtel</wicri:noRegion></affiliation></author><author><name sortKey="Vanscheeuwijck, Patrick" sort="Vanscheeuwijck, Patrick" uniqKey="Vanscheeuwijck P" first="Patrick" last="Vanscheeuwijck">Patrick Vanscheeuwijck</name><affiliation wicri:level="1"><nlm:affiliation>PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>PMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel</wicri:regionArea><wicri:noRegion>CH-2000 Neuchâtel</wicri:noRegion></affiliation></author></analytic><series><title level="j">Toxicology in vitro : an international journal published in association with BIBRA</title><idno type="eISSN">1879-3177</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Biological Assay</term><term>Cell Line</term><term>Cell Survival (drug effects)</term><term>Electronic Nicotine Delivery Systems</term><term>Humans</term><term>Lysosomes (metabolism)</term><term>Mice</term><term>Neutral Red (metabolism)</term><term>Nicotine (toxicity)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Dosage biologique</term><term>Humains</term><term>Lignée cellulaire</term><term>Lysosomes (métabolisme)</term><term>Nicotine (toxicité)</term><term>Rouge neutre (métabolisme)</term><term>Souris</term><term>Survie cellulaire ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Neutral Red</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Survival</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lysosomes</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Lysosomes</term><term>Rouge neutre</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Nicotine</term></keywords><keywords scheme="MESH" qualifier="toxicité" xml:lang="fr"><term>Nicotine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Biological Assay</term><term>Cell Line</term><term>Electronic Nicotine Delivery Systems</term><term>Humans</term><term>Mice</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Dosage biologique</term><term>Humains</term><term>Lignée cellulaire</term><term>Souris</term><term>Survie cellulaire</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Cytotoxicity assays are used to quantify the cytotoxic potential of chemicals. The neutral red uptake (NRU) assay is one of these assays and is routinely used in the pharmaceutical, cosmetic, and tobacco industries. In the context of e-cigarette development, an NRU assay-based screen was implemented to evaluate the cytotoxic potential of e-liquids. E-liquids induced a biphasic response in the BALB/c 3T3-based assay. The NRU initially increased in a concentration-dependent manner before decreasing following treatment with higher concentrations until NRU was abolished. Experiments were performed to characterize the mechanism underlying this biphasic signal. Nicotine alone was found to induce the same biphasic effects, while inducing concentration-dependent decreases in relative cell counts (RCC). Imaging and flow cytometry data revealed that the increases in NRU likely resulted from nicotine-induced vacuolization via a lysosomotropic mechanism. In support of this, two lysosomotropic agents, chloroquine and lapatinib, induced similar profiles. Nicotine's effects were also translatable, as brain-, lung-, bone marrow-, and smooth muscle-derived mammalian cells responded with the biphasic NRU signal. However, like RCC, three other cytotoxicity endpoints, resazurin, adenosine triphosphate, and water soluble tetrazolium salt (WST)-8, were not subject to these effects. The WST-8 assay is proposed as an alternative to screen the cytotoxic potential of e-liquids.</div></front></TEI><affiliations><list><country><li>Suisse</li></country></list><tree><country name="Suisse"><noRegion><name sortKey="Cudazzo, Gianluca" sort="Cudazzo, Gianluca" uniqKey="Cudazzo G" first="Gianluca" last="Cudazzo">Gianluca Cudazzo</name></noRegion><name sortKey="Mchugh, Damian" sort="Mchugh, Damian" uniqKey="Mchugh D" first="Damian" last="Mchugh">Damian Mchugh</name><name sortKey="Smart, Daniel J" sort="Smart, Daniel J" uniqKey="Smart D" first="Daniel J" last="Smart">Daniel J. Smart</name><name sortKey="Vanscheeuwijck, Patrick" sort="Vanscheeuwijck, Patrick" uniqKey="Vanscheeuwijck P" first="Patrick" last="Vanscheeuwijck">Patrick Vanscheeuwijck</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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