title: Investigation of the genotoxicity of quinocetone, carbadox and olaquindox in vitro using Vero cells.
abstract: Quinoxaline-1,4-dioxides derivatives have been widely used as animal growth promoter. This study was conducted to investigate the cytotoxicity and genotoxicity of quinoxaline-1,4-dioxides derivatives, namely carbadox, olaquindox and quinocetone, in Vero cells. The cell viability results from MTT assay demonstrated the severe inhibitory effects by these chemicals in both dose and time dependent manner. Among these chemicals quinocetone exhibited the highest cytotoxicity followed by olaquindox and carbadox. DNA damage analyses using alkalic comet assay revealed pronounced increase of DNA fragmentation in all three compound treated cells. In contrast, DNA damage was significantly decreased after incubation with S9 mix. These findings suggest that the intermediate metabolites of these compounds exerted lower genotoxicity than their parent drugs. We further described chromosomal damage induced by these drugs employing cytokinesis-block micronucleus assay (MN assays). The micronucleus frequency was significantly higher in these drugs treated cells than that of controls and the nuclear division index was also markedly reduced with increasing drug concentration applied. Similar to the observation in comet assay, incorporation of S9 mix in the MN assays was able to markedly alleviate the chromosome damage. In conclusion, our results strengthened previous reports on the cytotoxicity and genotoxicity of carbadox, olaquindox and quinocetone.
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.forename: Shusheng
authors.initials: S
authors.lastname: Tang
authors.forename: Xi
authors.initials: X
authors.lastname: Jin
authors.forename: Jiajie
authors.initials: J
authors.lastname: Zou
authors.forename: Kaipao
authors.initials: K
authors.lastname: Chen
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Xilong
authors.initials: X
authors.lastname: Xiao
mesh_terms: D000818:Animals; D002218:Carbadox / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D020552:Comet Assay; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005562:Formazans / Q000378:metabolism; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D015162:Micronucleus Tests; D008862:Microsomes, Liver; D008938:Mitosis / Q000187:drug effects; D009153:Mutagens / Q000633:toxicity*; D011810:Quinoxalines / Q000633:toxicity*; D013778:Tetrazolium Salts / Q000378:metabolism; D014709:Vero Cells
chemical_list: D005562:Formazans; D009153:Mutagens; D011810:Quinoxalines; D013778:Tetrazolium Salts; C502851:quinocetone; C079782:MTT formazan; D004247:DNA; C013168:olaquindox; D002218:Carbadox