title: Assessment of genotoxic effects of (4-methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone in human lymphocytes.
abstract: (4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (PHT) belongs to the phenstatin family. This compound has been studied due to its potent cytotoxicity and ability to inhibit tubulin assembly. The present study aimed to evaluate the mutagenic potential of PHT in human lymphocytes. PHT displayed cytotoxicity in human lymphocytes with an IC50 value of 5.68 μM, and therefore, concentrations of 0.25, 0.5, 1.0, 2.0, and 4.0 μM were used for all protocols. The alkaline comet assay and chromosome aberration (CA) analysis were performed in different phases of the cell cycle (G1, G1/S, transition, and G2), to evaluate the DNA-damaging and clastogenic effects of PHT, respectively. CA analysis was carried out in the presence or absence of colchicine to evaluate the action of PHT in the mitotic phase. PHT was cytotoxic and significantly reduced the mitotic index with drug exposure in all phases of cell cycle. Interestingly, it induced an increase in mitotic index in experimental protocols without colchicine, corroborating its action as an antitubulin agent. It also induced DNA damage and was clastogenic with drug exposure in all phases of the cell cycle, in the presence or absence of colchicine. In conclusion, PHT induces DNA damage and exerts clastogenic effects in human lymphocytes.
authors.affiliation: Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Hemerson I F
authors.initials: HI
authors.lastname: Magalhães
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Cavalcanti
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Bezerra
authors.forename: Diego V
authors.initials: DV
authors.lastname: Wilke
authors.forename: Jean C G
authors.initials: JC
authors.lastname: Paiva
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Rotta
authors.forename: Dênis P
authors.initials: DP
authors.lastname: de Lima
authors.forename: Adilson
authors.initials: A
authors.lastname: Beatriz
authors.forename: Rommel R
authors.initials: RR
authors.lastname: Burbano
authors.forename: Letícia V
authors.initials: LV
authors.lastname: Costa-Lotufo
authors.forename: Manoel Odorico
authors.initials: MO
authors.lastname: Moraes
authors.forename: Claudia
authors.initials: C
authors.lastname: Pessoa
mesh_terms: D000328:Adult; D001577:Benzophenones / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000139:chemically induced*; D020552:Comet Assay; D004249:DNA Damage; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D055815:Young Adult
chemical_list: C560639:(4-methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone; D001577:Benzophenones; D009153:Mutagens