Differential toxicity of abrin in human cell lines of different organ origin

Abrus precatorius is a highly toxic seed containing the poison abrin. Similar in properties to ricin, this toxin binds to ribosomes causing cessation of protein synthesis and cell death. With an estimated human lethal dose of 0.1–1 μg/kg, it has been the cause of fatalities due to accidental and int...

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Veröffentlicht in:Toxicology in vitro 2022-02, Vol.78, p.105250-105250, Article 105250
Hauptverfasser: Saxena, Nandita, Phatak, Pooja, Chauhan, Vinita
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Chauhan, Vinita
description Abrus precatorius is a highly toxic seed containing the poison abrin. Similar in properties to ricin, this toxin binds to ribosomes causing cessation of protein synthesis and cell death. With an estimated human lethal dose of 0.1–1 μg/kg, it has been the cause of fatalities due to accidental and intentional ingestion. In present study, we profiled seven human cell lines of different organ origin, for their sensitivity against abrin toxicity. These cell lines are, A549, COLO 205, HEK 293, HeLa, Hep G2, Jurkat, SH-SY5Y and derived from lung, intestine, kidney, cervix, liver, immune and nervous system respectively. MTT, NR, CVDE and LDH assays have been used to determine their response against abrin toxin. Among these cell lines A549 was the most sensitive cell line while Hep G2 was found least sensitive cell lines. Hep G2 cells are shown to have mitochondrial resistance and delayed generation of oxidative stress compared to A549 cells. Remarkable variation in sensitivity against abrin toxicity prompted the evaluation of Bcl2, Bax and downstream caspases in both cells. Difference in Bcl2 level has been shown to play important role in variable sensitivity. Findings of present study are helpful for selection of suitable cellular model for toxicity assessment and antidote screening. [Display omitted] •Abrin is potential bioweapon and many folds toxin than ricin a schedule 1 agents.•Investigations of abrin required suitable cellular model to reduce the animal usage.•Among seven cell lines, A549 was the most sensitive and Hep G2 was found to be the least sensitive cell line.•Bcl2 protein play major role in differential sensitivity.•Study may helpful for toxicity assessment and antidote screening.
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Similar in properties to ricin, this toxin binds to ribosomes causing cessation of protein synthesis and cell death. With an estimated human lethal dose of 0.1–1 μg/kg, it has been the cause of fatalities due to accidental and intentional ingestion. In present study, we profiled seven human cell lines of different organ origin, for their sensitivity against abrin toxicity. These cell lines are, A549, COLO 205, HEK 293, HeLa, Hep G2, Jurkat, SH-SY5Y and derived from lung, intestine, kidney, cervix, liver, immune and nervous system respectively. MTT, NR, CVDE and LDH assays have been used to determine their response against abrin toxin. Among these cell lines A549 was the most sensitive cell line while Hep G2 was found least sensitive cell lines. Hep G2 cells are shown to have mitochondrial resistance and delayed generation of oxidative stress compared to A549 cells. Remarkable variation in sensitivity against abrin toxicity prompted the evaluation of Bcl2, Bax and downstream caspases in both cells. Difference in Bcl2 level has been shown to play important role in variable sensitivity. Findings of present study are helpful for selection of suitable cellular model for toxicity assessment and antidote screening. [Display omitted] •Abrin is potential bioweapon and many folds toxin than ricin a schedule 1 agents.•Investigations of abrin required suitable cellular model to reduce the animal usage.•Among seven cell lines, A549 was the most sensitive and Hep G2 was found to be the least sensitive cell line.•Bcl2 protein play major role in differential sensitivity.•Study may helpful for toxicity assessment and antidote screening.</description><identifier>ISSN: 0887-2333</identifier><identifier>EISSN: 1879-3177</identifier><identifier>DOI: 10.1016/j.tiv.2021.105250</identifier><identifier>PMID: 34601064</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>A549 cells ; Abrin ; Abrin - toxicity ; Abrus - chemistry ; Antidotes ; Bax protein ; bcl-2-Associated X Protein - metabolism ; Caspases - metabolism ; Cell death ; Cell Line - drug effects ; Cell lines ; Cell Survival - drug effects ; Cytotoxicity ; Differential sensitivity ; Hep G2 cells ; Humans ; Ingestion ; Intestine ; L-Lactate Dehydrogenase - drug effects ; Lethal dose ; Lysosomes - drug effects ; Membrane Potential, Mitochondrial - drug effects ; Mitochondria ; Nervous system ; Oxidation resistance ; Oxidative stress ; Protein biosynthesis ; Protein synthesis ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Reactive Oxygen Species - metabolism ; Ribosomes ; Ricin ; Toxicity ; Toxins</subject><ispartof>Toxicology in vitro, 2022-02, Vol.78, p.105250-105250, Article 105250</ispartof><rights>2021 Elsevier Ltd</rights><rights>Copyright © 2021 Elsevier Ltd. 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Similar in properties to ricin, this toxin binds to ribosomes causing cessation of protein synthesis and cell death. With an estimated human lethal dose of 0.1–1 μg/kg, it has been the cause of fatalities due to accidental and intentional ingestion. In present study, we profiled seven human cell lines of different organ origin, for their sensitivity against abrin toxicity. These cell lines are, A549, COLO 205, HEK 293, HeLa, Hep G2, Jurkat, SH-SY5Y and derived from lung, intestine, kidney, cervix, liver, immune and nervous system respectively. MTT, NR, CVDE and LDH assays have been used to determine their response against abrin toxin. Among these cell lines A549 was the most sensitive cell line while Hep G2 was found least sensitive cell lines. Hep G2 cells are shown to have mitochondrial resistance and delayed generation of oxidative stress compared to A549 cells. Remarkable variation in sensitivity against abrin toxicity prompted the evaluation of Bcl2, Bax and downstream caspases in both cells. Difference in Bcl2 level has been shown to play important role in variable sensitivity. Findings of present study are helpful for selection of suitable cellular model for toxicity assessment and antidote screening. 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Similar in properties to ricin, this toxin binds to ribosomes causing cessation of protein synthesis and cell death. With an estimated human lethal dose of 0.1–1 μg/kg, it has been the cause of fatalities due to accidental and intentional ingestion. In present study, we profiled seven human cell lines of different organ origin, for their sensitivity against abrin toxicity. These cell lines are, A549, COLO 205, HEK 293, HeLa, Hep G2, Jurkat, SH-SY5Y and derived from lung, intestine, kidney, cervix, liver, immune and nervous system respectively. MTT, NR, CVDE and LDH assays have been used to determine their response against abrin toxin. Among these cell lines A549 was the most sensitive cell line while Hep G2 was found least sensitive cell lines. Hep G2 cells are shown to have mitochondrial resistance and delayed generation of oxidative stress compared to A549 cells. Remarkable variation in sensitivity against abrin toxicity prompted the evaluation of Bcl2, Bax and downstream caspases in both cells. Difference in Bcl2 level has been shown to play important role in variable sensitivity. Findings of present study are helpful for selection of suitable cellular model for toxicity assessment and antidote screening. [Display omitted] •Abrin is potential bioweapon and many folds toxin than ricin a schedule 1 agents.•Investigations of abrin required suitable cellular model to reduce the animal usage.•Among seven cell lines, A549 was the most sensitive and Hep G2 was found to be the least sensitive cell line.•Bcl2 protein play major role in differential sensitivity.•Study may helpful for toxicity assessment and antidote screening.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>34601064</pmid><doi>10.1016/j.tiv.2021.105250</doi><tpages>1</tpages></addata></record>
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1879-3177
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subjects A549 cells
Abrin
Abrin - toxicity
Abrus - chemistry
Antidotes
Bax protein
bcl-2-Associated X Protein - metabolism
Caspases - metabolism
Cell death
Cell Line - drug effects
Cell lines
Cell Survival - drug effects
Cytotoxicity
Differential sensitivity
Hep G2 cells
Humans
Ingestion
Intestine
L-Lactate Dehydrogenase - drug effects
Lethal dose
Lysosomes - drug effects
Membrane Potential, Mitochondrial - drug effects
Mitochondria
Nervous system
Oxidation resistance
Oxidative stress
Protein biosynthesis
Protein synthesis
Proto-Oncogene Proteins c-bcl-2 - metabolism
Reactive Oxygen Species - metabolism
Ribosomes
Ricin
Toxicity
Toxins
title Differential toxicity of abrin in human cell lines of different organ origin
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