title: 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.
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.
authors.affiliation: Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasilia, Brasilia/DF 70.910-900, Brazil. belinpmezzomo@yahoo.com.br.
authors.forename: Bélin Poletto
authors.initials: BP
authors.lastname: Mezzomo
authors.affiliation: Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasilia, Brasilia/DF 70.910-900, Brazil. mirandavilela@unb.br.|Faculty of Medicine, Faciplac, Campus Gama, SIGA Área Especial N° 02 Setor Leste-Gama/DF 72.460-000, Brazil. mirandavilela@unb.br.
authors.forename: Ana Luisa
authors.initials: AL
authors.lastname: Miranda-Vilela
authors.affiliation: Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasilia, Brasilia/DF 70.910-900, Brazil. grisolia@unb.br.
authors.forename: Cesar Koppe
authors.initials: CK
authors.lastname: Grisolia
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D054314:Drug Inverse Agonism; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006403:Hematologic Tests; D006460:Hemolysin Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D009092:Mucous Membrane; D013171:Spores, Bacterial
chemical_list: D000276:Adjuvants, Immunologic; D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins; D004731:Endotoxins; D006460:Hemolysin Proteins; C030956:insecticidal crystal protein, Bacillus Thuringiensis
keywords: Bacillus thuringiensis; Cry1Ac toxin; biosafety; genotoxicity; hematoxicicity; δ-endotoxins