Cytotoxic and genotoxic effects of cylindrospermopsin in mice treated by gavage or intraperitoneal injection
Identifieur interne : 001845 ( Istex/Corpus ); précédent : 001844; suivant : 001846Cytotoxic and genotoxic effects of cylindrospermopsin in mice treated by gavage or intraperitoneal injection
Auteurs : Emmanuelle Bazin ; Sylvie Huet ; Gérard Jarry ; Ludovic Le Hégarat ; John S. Munday ; Andrew R. Humpage ; Valérie FessardSource :
- Environmental Toxicology [ 1520-4081 ] ; 2012-05.
English descriptors
- KwdEn :
- Alga cylindrospermopsis raciborskii, Alkaline comet assay, Anabaena lapponica, Apoptosis, Apoptotic, Apoptotic cells, Assay, Australian water quality center, Bone marrow, Bone marrow cells, Cell death, Cell suspensions, Colon, Colon cells, Colonic cells, Comet, Comet assay, Corticomedullary junction, Cyanobacterial, Cyanobacterial toxin, Cylindrospermopsin, Cylindrospermopsis, Cylindrospermopsis raciborskii, Cytotoxic, Cytotoxic effects, Cytotoxicity, Dead cells, Dos, Environ, Environmental toxicology, Epithelial, Erythrocyte, Falconer, First report, Gastrointestinal tract, Gavage, Genotoxic, Genotoxic effects, Genotoxicity, Hbss medium, Histological, Histological examination, Histological lesions, Humpage, Intraperitoneal, Intraperitoneal injection route, Liquid stools, Lyngbya wollei, Median, Metabolic activation, Methyl methane sulfonate, Micronucleated, Micronucleus, Micronucleus assay, Micronucleus test, Mitotic cells, Mouse, Mouse tissues, Multiple foci, Mutat, Negative control, Normochromatic erythrocytes, Norris, Oral administration, Oral dose, Oral dosing, Oral exposure, Oral toxicity, Physiological saline, Polychromatic erythrocytes, Positive control, Preliminary evidence, Previous studies, Raciborskii, Raphidiopsis curvata, Rodent genotoxicity assays, Room temperature, Seawright, Sodium pentobarbital, Statistical analysis, Target organs, Toxicity, Toxicol, Toxicology, Toxin, Treatment group, Tubular epithelial cells, Water supplies, Wiley periodicals.
- Teeft :
- Alga cylindrospermopsis raciborskii, Alkaline comet assay, Anabaena lapponica, Apoptosis, Apoptotic, Apoptotic cells, Assay, Australian water quality center, Bone marrow, Bone marrow cells, Cell death, Cell suspensions, Colon, Colon cells, Colonic cells, Comet, Comet assay, Corticomedullary junction, Cyanobacterial, Cyanobacterial toxin, Cylindrospermopsin, Cylindrospermopsis, Cylindrospermopsis raciborskii, Cytotoxic, Cytotoxic effects, Cytotoxicity, Dead cells, Dos, Environ, Environmental toxicology, Epithelial, Erythrocyte, Falconer, First report, Gastrointestinal tract, Gavage, Genotoxic, Genotoxic effects, Genotoxicity, Hbss medium, Histological, Histological examination, Histological lesions, Humpage, Intraperitoneal, Intraperitoneal injection route, Liquid stools, Lyngbya wollei, Median, Metabolic activation, Methyl methane sulfonate, Micronucleated, Micronucleus, Micronucleus assay, Micronucleus test, Mitotic cells, Mouse, Mouse tissues, Multiple foci, Mutat, Negative control, Normochromatic erythrocytes, Norris, Oral administration, Oral dose, Oral dosing, Oral exposure, Oral toxicity, Physiological saline, Polychromatic erythrocytes, Positive control, Preliminary evidence, Previous studies, Raciborskii, Raphidiopsis curvata, Rodent genotoxicity assays, Room temperature, Seawright, Sodium pentobarbital, Statistical analysis, Target organs, Toxicity, Toxicol, Toxicology, Toxin, Treatment group, Tubular epithelial cells, Water supplies, Wiley periodicals.
Abstract
Cylindrospermopsin (CYN), a cyanobacterial hepatotoxin mainly produced by Cylindrospermopsis raciborskii, has been involved in human intoxications and livestock deaths. The widespread occurrence of CYN in the water supplies lead us to investigate its genotoxicity to assess potential chronic effects. This study reports evaluation of CYN‐induced in vivo DNA damage in mice using alkaline comet assay (ACA) and micronucleus assay (MNA) concomittantly. ACA measures DNA breakage from single and double strand breaks as well as alkali labile sites. Conversely, MNA detects chromosome damage events such as chromosomal breakage and numeric alterations. Male Swiss mice were treated with CYN concentrations of 50, 100, and 200 μg/kg by a single intraperitoneal (ip) injection or with 1, 2, and 4 mg/kg by gavage. Methyl methane sulfonate (MMS) was used as positive control at 80 mg/kg. Twenty‐four hours after treatment, samples of liver, blood, bone marrow, kidney, intestine, and colon were taken to perform ACA, the bone marrow and the colon were also used for MNA. Parameters used to quantify DNA damage were % Tail DNA for ACA and both micronucleated immature erythrocytes and epithelial colon cells for MNA. DNA breaks and chromosome damage were significantly increased by MMS in all the organs evaluated. Significant DNA damage was detected within the colon by ACA after ip injection of 100 and 200 μg/kg CYN (P < 0.01). DNA damage was also detected in colon samples after 4 mg/kg oral administration of CYN and in bone marrow after 1 and 2 mg/kg of orally administered CYN. Histological examination showed foci of cell death within the liver and the kidney from mice that received the two highest doses of CYN by either route of administration. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.
Url:
DOI: 10.1002/tox.20640
Links to Exploration step
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<term>Oral dose</term>
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<term>Anabaena lapponica</term>
<term>Apoptosis</term>
<term>Apoptotic</term>
<term>Apoptotic cells</term>
<term>Assay</term>
<term>Australian water quality center</term>
<term>Bone marrow</term>
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<term>Preliminary evidence</term>
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<front><div type="abstract" xml:lang="en">Cylindrospermopsin (CYN), a cyanobacterial hepatotoxin mainly produced by Cylindrospermopsis raciborskii, has been involved in human intoxications and livestock deaths. The widespread occurrence of CYN in the water supplies lead us to investigate its genotoxicity to assess potential chronic effects. This study reports evaluation of CYN‐induced in vivo DNA damage in mice using alkaline comet assay (ACA) and micronucleus assay (MNA) concomittantly. ACA measures DNA breakage from single and double strand breaks as well as alkali labile sites. Conversely, MNA detects chromosome damage events such as chromosomal breakage and numeric alterations. Male Swiss mice were treated with CYN concentrations of 50, 100, and 200 μg/kg by a single intraperitoneal (ip) injection or with 1, 2, and 4 mg/kg by gavage. Methyl methane sulfonate (MMS) was used as positive control at 80 mg/kg. Twenty‐four hours after treatment, samples of liver, blood, bone marrow, kidney, intestine, and colon were taken to perform ACA, the bone marrow and the colon were also used for MNA. Parameters used to quantify DNA damage were % Tail DNA for ACA and both micronucleated immature erythrocytes and epithelial colon cells for MNA. DNA breaks and chromosome damage were significantly increased by MMS in all the organs evaluated. Significant DNA damage was detected within the colon by ACA after ip injection of 100 and 200 μg/kg CYN (P < 0.01). DNA damage was also detected in colon samples after 4 mg/kg oral administration of CYN and in bone marrow after 1 and 2 mg/kg of orally administered CYN. Histological examination showed foci of cell death within the liver and the kidney from mice that received the two highest doses of CYN by either route of administration. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.</div>
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<p>Cylindrospermopsin (CYN), a cyanobacterial hepatotoxin mainly produced by <hi rend="italic">Cylindrospermopsis raciborskii</hi>
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<keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">cylindrospermopsin</keyword>
<keyword xml:id="kwd2">genotoxicity</keyword>
<keyword xml:id="kwd3"><i>in vivo</i>
alkaline comet assay</keyword>
<keyword xml:id="kwd4"><i>in vivo</i>
micronucleus assay</keyword>
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<p>Cylindrospermopsin (CYN), a cyanobacterial hepatotoxin mainly produced by <i>Cylindrospermopsis raciborskii</i>
, has been involved in human intoxications and livestock deaths. The widespread occurrence of CYN in the water supplies lead us to investigate its genotoxicity to assess potential chronic effects. This study reports evaluation of CYN‐induced <i>in vivo</i>
DNA damage in mice using alkaline comet assay (ACA) and micronucleus assay (MNA) concomittantly. ACA measures DNA breakage from single and double strand breaks as well as alkali labile sites. Conversely, MNA detects chromosome damage events such as chromosomal breakage and numeric alterations. Male Swiss mice were treated with CYN concentrations of 50, 100, and 200 μg/kg by a single intraperitoneal (ip) injection or with 1, 2, and 4 mg/kg by gavage. Methyl methane sulfonate (MMS) was used as positive control at 80 mg/kg. Twenty‐four hours after treatment, samples of liver, blood, bone marrow, kidney, intestine, and colon were taken to perform ACA, the bone marrow and the colon were also used for MNA. Parameters used to quantify DNA damage were % Tail DNA for ACA and both micronucleated immature erythrocytes and epithelial colon cells for MNA. DNA breaks and chromosome damage were significantly increased by MMS in all the organs evaluated. Significant DNA damage was detected within the colon by ACA after ip injection of 100 and 200 μg/kg CYN (<i>P</i>
< 0.01). DNA damage was also detected in colon samples after 4 mg/kg oral administration of CYN and in bone marrow after 1 and 2 mg/kg of orally administered CYN. Histological examination showed foci of cell death within the liver and the kidney from mice that received the two highest doses of CYN by either route of administration. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.</p>
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<name type="personal"><namePart type="given">Emmanuelle</namePart>
<namePart type="family">Bazin</namePart>
<affiliation>Agence Française de Sécurité Sanitaire des Aliments, Unité de Toxicologie Génétique des Contaminants Alimentaires, BP 90 203, 35 302 Fougères Cedex, France</affiliation>
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<name type="personal"><namePart type="given">Gérard</namePart>
<namePart type="family">Jarry</namePart>
<affiliation>Agence Française de Sécurité Sanitaire des Aliments, Unité de Toxicologie Génétique des Contaminants Alimentaires, BP 90 203, 35 302 Fougères Cedex, France</affiliation>
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<name type="personal"><namePart type="given">Ludovic Le</namePart>
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<name type="personal"><namePart type="given">Andrew R.</namePart>
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<affiliation>E-mail: valerie.fessard@anses.fr</affiliation>
<affiliation>Correspondence address: Agence Française de Sécurité Sanitaire des Aliments, Unité de Toxicologie Génétique des Contaminants Alimentaires, BP 90 203, 35 302 Fougères Cedex, France</affiliation>
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<abstract lang="en">Cylindrospermopsin (CYN), a cyanobacterial hepatotoxin mainly produced by Cylindrospermopsis raciborskii, has been involved in human intoxications and livestock deaths. The widespread occurrence of CYN in the water supplies lead us to investigate its genotoxicity to assess potential chronic effects. This study reports evaluation of CYN‐induced in vivo DNA damage in mice using alkaline comet assay (ACA) and micronucleus assay (MNA) concomittantly. ACA measures DNA breakage from single and double strand breaks as well as alkali labile sites. Conversely, MNA detects chromosome damage events such as chromosomal breakage and numeric alterations. Male Swiss mice were treated with CYN concentrations of 50, 100, and 200 μg/kg by a single intraperitoneal (ip) injection or with 1, 2, and 4 mg/kg by gavage. Methyl methane sulfonate (MMS) was used as positive control at 80 mg/kg. Twenty‐four hours after treatment, samples of liver, blood, bone marrow, kidney, intestine, and colon were taken to perform ACA, the bone marrow and the colon were also used for MNA. Parameters used to quantify DNA damage were % Tail DNA for ACA and both micronucleated immature erythrocytes and epithelial colon cells for MNA. DNA breaks and chromosome damage were significantly increased by MMS in all the organs evaluated. Significant DNA damage was detected within the colon by ACA after ip injection of 100 and 200 μg/kg CYN (P < 0.01). DNA damage was also detected in colon samples after 4 mg/kg oral administration of CYN and in bone marrow after 1 and 2 mg/kg of orally administered CYN. Histological examination showed foci of cell death within the liver and the kidney from mice that received the two highest doses of CYN by either route of administration. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.</abstract>
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