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Toxins 2015, 7(12), 5348-5358; doi:10.3390/toxins7124881

Toxicological Evaluation of a Potential Immunosensitizer for Use as a Mucosal Adjuvant—Bacillus thuringiensis Cry1Ac Spore-Crystals: A Possible Inverse Agonist that Deserves Further Investigation

1
Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasilia, Brasilia/DF 70.910-900, Brazil
2
Faculty of Medicine, Faciplac, Campus Gama, SIGA Área Especial N° 02 Setor Leste—Gama/DF 72.460-000, Brazil
*
Authors to whom correspondence should be addressed.
Academic Editor: Vernon L. Tesh
Received: 14 August 2015 / Revised: 15 September 2015 / Accepted: 9 October 2015 / Published: 9 December 2015
(This article belongs to the Section Bacterial Toxins)
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Abstract

In addition to their applicability as biopesticides, Bacillus thuringiensis (Bt) Cry1Ac spore-crystals are being researched in the immunology field for their potential as adjuvants in mucosal and parenteral immunizations. We aimed to investigate the hematotoxicity and genotoxicity of Bt spore-crystals genetically modified to express Cry1Ac individually, administered orally (p.o.) or with a single intraperitoneal (i.p.) injection 24 h before euthanasia, to simulate the routes of mucosal and parenteral immunizations in Swiss mice. Blood samples were used to perform hemogram, and bone marrow was used for the micronucleus test. Cry1Ac presented cytotoxic effects on erythroid lineage in both routes, being more severe in the i.p. route, which also showed genotoxic effects. The greater severity noted in this route, mainly at 6.75 mg/kg, as well as the intermediate effects at 13.5 mg/kg, and the very low hematotoxicity at 27 mg/kg, suggested a possible inverse agonism. The higher immunogenicity for the p.o. route, particularly at 27 mg/kg, suggested that at this dose, Cry 1Ac could potentially be used as a mucosal adjuvant (but not in parenteral immunizations, due to the genotoxic effects observed). This potential should be investigated further, including making an evaluation of the proposed inverse agonism and carrying out cytokine profiling. View Full-Text
Keywords: Bacillus thuringiensis; δ-endotoxins; Cry1Ac toxin; biosafety; hematoxicicity; genotoxicity Bacillus thuringiensis; δ-endotoxins; Cry1Ac toxin; biosafety; hematoxicicity; genotoxicity
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Mezzomo, B.P.; Miranda-Vilela, A.L.; Grisolia, C.K. Toxicological Evaluation of a Potential Immunosensitizer for Use as a Mucosal Adjuvant—Bacillus thuringiensis Cry1Ac Spore-Crystals: A Possible Inverse Agonist that Deserves Further Investigation. Toxins 2015, 7, 5348-5358.

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