title: Genotoxic and Mutagenic Activity of PT-31.
abstract: Toxicity assessment is an important tool in drug discovery and development. PT-31 (3-(2-chloro-6-fluorobenzyl)-imidazolidine-2,4-dione) is an imidazolidine- 2,4-dione analogue of clonidine that displays a dose-dependent analgesic profile and synergism with morphine. This study investigated genotoxic and mutagenic effects of PT-31 in Swiss mice. For this, ten mice (M1:F1) per group were treated with PT-31 intraperitoneally (i.p.) at 0.5, 1.0 and 5.0 mg/kg. The dimethyl sulfoxide (0.5%) and 50 mg/kg cyclophosphamide (i.p.) were taken as negative (NC) and positive controls, respectively. The bone marrow cells were collected after 24 h, while peripheral blood after 30 min, 12 h and 24 h of the treatment for the comet assay. Micronucleus (MN) test was performed only on bone marrow cells collected after 24 h of i.p. treated animals. A hundred cells were considered for the comet assay and quantification of the index of damage and frequency of damage. Lack of genotoxicity with 0.5 mg/kg of PT-31 and DNA repair ability with 0.5 and 1.0 mg/kg doses at 12 h and 24 h in comparison to NC group was observed (P<0.05). There was an increase in MN formation by PT-31 1.0 and 5.0 mg/kg treated female and male mice, respectively. PT-31 induced genotoxic and mutagenic effects only in higher doses.
authors.forename: Manoel P L
authors.initials: MP
authors.lastname: Neto
authors.forename: Débora C V
authors.initials: DC
authors.lastname: Gomes
authors.forename: Antonio L G
authors.initials: AL
authors.lastname: Júnior
authors.forename: Márcia F C J
authors.initials: MF
authors.lastname: Paz
authors.forename: Marcus V O B
authors.initials: MV
authors.lastname: Alencar
authors.affiliation: Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina (Piauí)-64.049-550, Brazil.
authors.forename: Md T
authors.initials: MT
authors.lastname: Islam
authors.forename: Paulo M P
authors.initials: PM
authors.lastname: Ferreira
authors.forename: Ana A C
authors.initials: AA
authors.lastname: Melo-Cavalcante
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects*; D020552:Comet Assay; D003520:Cyclophosphamide / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D048289:Imidazolidines / Q000494:pharmacology; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens
chemical_list: C549017:3-(2-chloro-6-fluorobenzyl)-imidazolidine-2,4-dione; D048289:Imidazolidines; D009153:Mutagens; D003520:Cyclophosphamide; D004121:Dimethyl Sulfoxide