A case of drug-induced hematotoxicity: from in vivo to in vitro assessment

Beamonte, A.; Goldfain-Blanc, Françoise; Casadevall, Nicole; Bazot, D.; Bertheux, H.; Claude, Nancy

doi:10.1007/s00580-005-0549-3

Cited by 4 publications

(2 citation statements)

References 8 publications

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“…Some substances that act on bone marrow may have a selective effect, that is, they may be toxic to a given cell line [35]. Our study found selective cytotoxicity for the erythroid lineage and showed differences in the dose response curves of Bt spore-crystals genetically modified to express individually Cry1Aa, Cry1Ab, Cry1Ac or Cry2A.…”

Section: Discussionmentioning

confidence: 54%

Hematotoxicity of Bacillus thuringiensis as Spore-crystal Strains Cry1Aa, Cry1Ab, Cry1Ac or Cry2Aa in Swiss Albino Mice

Mezzomo¹,

Miranda-Vilela²,

Freire³

et al. 2013

J Hematol Thrombo Diseases

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al. Este é um artigo de acesso aberto distribuído sob os termos da Licença de Atribuição Creative Commons, que permite uso irrestrito, distribuição e reprodução em qualquer meio, desde que o autor e a fonte originais são creditados . Journal of Hematology & Thromboembolic DiseasesResearch Article Open Access AbstractFormulated and sporulated cultures of Bacillus thuringiensis (Bt) have been widely used against insect pests, but after the advent of genetically modified plants expressing δ-endotoxins, the bioavailability of Cry proteins has been increased. For biosafety reasons their adverse effects should be studied, mainly for non-target organisms. Thus, we evaluated, in Swiss albino mice, the hematotoxicity and genotoxicity of four Bt spore-crystals genetically modified to express individually Cry1Aa, Cry1Ab, Cry1Ac or Cry2A, administered alone by gavage with a single dose of 27 mg/ Kg, 136 mg/Kg or 270 mg/Kg, 24 h, 72 h or 7 days before euthanasia. Binary combinations of these four spore-crystal proteins were also assayed at 270 mg/Kg with a single administration 24 h before euthanasia. Control mice received filtered water or cyclophosphamide at 27 mg/kg. For hematotoxicity evaluations, blood samples were drawn by cardiac puncture and processed in a multiple automated hematology analyzer; for genotoxicity analyses, micronucleus test was carried out in mice bone marrow cells. Spore-crystal administrations provoked selective hematotoxicity for the 3 exposure times, particularly for erythroid lineage. A significant reduction in bone marrow cell proliferation demonstrated cytotoxic but not genotoxic effects. These effects persisted for all exposure times, becoming more evident at 7 days. Similar results were observed for binary combinations at 24 h, suggesting that further studies are required to clarify the mechanism involved in the hematotoxicity found in mice, and to establish the toxicological risks to non-target organisms, especially mammals, before concluding that these microbiological control agents are safe for mammals.

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Section: Discussionmentioning

confidence: 54%

Hematotoxicity of Bacillus thuringiensis as Spore-crystal Strains Cry1Aa, Cry1Ab, Cry1Ac or Cry2Aa in Swiss Albino Mice

Mezzomo¹,

Miranda-Vilela²,

Freire³

et al. 2013

J Hematol Thrombo Diseases

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“…Because of its high mitotic index, hematopoietic tissue becomes the target of the adverse effects of many chemical substances entering the body. Some substances that act on bone marrow may have a selective effect, that is, they may be toxic to a given cell line (Beamonte et al, ). When depression in the bone marrow occurs, causing a drop in mitotic index (inhibition), many forms of normochromatic erythrocytes that should be removed from the bone marrow to the circulating blood, instead remain in the bone marrow.…”

Section: Discussionmentioning

confidence: 99%

Hematotoxicity and genotoxicity evaluations in Swiss mice intraperitoneally exposed to Bacillus thuringiensis (var kurstaki) spore crystals genetically modified to express individually Cry1Aa, Cry1Ab, Cry1Ac, or Cry2Aa

Mezzomo

Miranda-Vilela

Barbosa

et al. 2015

Environmental Toxicology

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Bacillus thuringiensis (Bt) has been widely used in foliar sprays as part of integrated pest management strategies against insect pests of agricultural crops. Since the advent of genetically modified plants expressing Bt δ-endotoxins, the bioavailability of Cry proteins has increased, and therefore for biosafety reasons their adverse effects should be studied, mainly for nontarget organisms. We evaluated, in Swiss mice, the hematotoxicity and genotoxicity of the genetically modified strains of Bt spore crystals Cry1Aa, 1Ab, 1Ac, or 2Aa at 27 mg/kg, and Cry1Aa, 1Ab and 2Aa also at 136 and 270 mg/kg, administered with a single intraperitoneal injection 24 h before euthanasia. Controls received filtered water or cyclophosphamide. Blood samples collected by cardiac puncture were used to perform hemogram, and bone marrow was extracted for the micronucleus test. Bt spore crystals presented toxicity for lymphocytes when in higher doses, which varied according to the type of spore crystal studied, besides promoting cytotoxic and genotoxic effects for the erythroid lineage of bone marrow, mainly at highest doses. Although the profile of such adverse side effects can be related to their high level of exposure, which is not commonly found in the environment, results indicated that these Bt spore crystals were not harmless to mice. This suggests that a more specific approach should be taken to increase knowledge about their toxicological properties and to establish the toxicological risks to nontarget organisms. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 970-978, 2016.

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Refinement and verification of test conditions for colony-forming unit assay in rat bone marrow cells with preservable colony specimens

et al. 2012

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A case of drug-induced hematotoxicity: from in vivo to in vitro assessment

Cited by 4 publications

References 8 publications

Hematotoxicity of Bacillus thuringiensis as Spore-crystal Strains Cry1Aa, Cry1Ab, Cry1Ac or Cry2Aa in Swiss Albino Mice

Hematotoxicity of Bacillus thuringiensis as Spore-crystal Strains Cry1Aa, Cry1Ab, Cry1Ac or Cry2Aa in Swiss Albino Mice

Hematotoxicity and genotoxicity evaluations in Swiss mice intraperitoneally exposed to Bacillus thuringiensis (var kurstaki) spore crystals genetically modified to express individually Cry1Aa, Cry1Ab, Cry1Ac, or Cry2Aa

Refinement and verification of test conditions for colony-forming unit assay in rat bone marrow cells with preservable colony specimens

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