title: Genotoxicity of quinocetone, cyadox and olaquindox in vitro and in vivo.
abstract: Quinocetone (QCT) and Cyadox (CYA) are important derivative of heterocyclic N-oxide quinoxaline (QdNO), used actively as antimicrobial feed additives in China. Here, we tested and compared the genotoxic potential of QCT and CYA with olaquindox (OLA) in Ames test, HGPRT gene mutation (HGM) test in V79 cells, unscheduled DNA synthesis (UDS) assay in human peripheral lymphocytes, chromosome aberration (CA) test, and micronucleus (MN) test in mice bone marrow. OLA was found genotoxic in all 5 assays. In Ames test, QCT produced His(+) mutants at 6.9 μg/plate in Salmonella typhimurium TA 97, at 18.2 μg/plate in TA 100, TA 1535, TA 1537, and at 50 μg/plate in TA 98. CYA produced His(+) mutants at 18.2 μg/plate in TA 97, TA 1535, and at 50 μg/plate in TA 98, TA 100 and TA 1537. QCT was found positive in HGM and UDS assay at concentrations ≥10 μg/ml while negative results were reported in CA test and MN test. Collectively, we found that OLA was more genotoxic than QCT and CYA. Genotoxicity of QCT was found at higher concentration levels in Ames test, HGM and UDS assays while CYA showed weak mutagenic potential to bacterial cells in Ames test.
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU), MOA Key Laboratory for the Detection of Veterinary Drug Residues in Foods, Huazhong Agricultural University, Wuhan, Hubei 430070, China. awais.dr@gmail.com
authors.forename: Awais
authors.initials: A
authors.lastname: Ihsan
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Honggang
authors.initials: H
authors.lastname: Tu
authors.forename: Yulian
authors.initials: Y
authors.lastname: Wang
authors.forename: Lingli
authors.initials: L
authors.lastname: Huang
authors.forename: Zahid
authors.initials: Z
authors.lastname: Iqbal
authors.forename: Guyue
authors.initials: G
authors.lastname: Cheng
authors.forename: Yuanhu
authors.initials: Y
authors.lastname: Pan
authors.forename: Zhenli
authors.initials: Z
authors.lastname: Liu
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Tan
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zonghui
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D009154:Mutation / Q000187:drug effects; D011810:Quinoxalines / Q000008:administration & dosage / Q000633:toxicity*; D011897:Random Allocation; D012486:Salmonella typhimurium / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D009153:Mutagens; D011810:Quinoxalines; C502851:quinocetone; C020728:cyadox; C013168:olaquindox
keywords: 4-Dioxides; 6-TG; 6-thioguanine; ATCC; American type culture collection; Ames; BaP; CA; CBX; CCTCC; CP; CYA; China Center for Type Culture Collection; Cyadox; Cyclophosphamide; DMEM; Dulbecco’s modified Eagle’s Medium; EMS; Genotoxicity; HAT; HGM; HGPRT gene mutation; MMC; MN; NCF; OLA; QCT; QdNOs; Quinocetone; Quinoxaline-1; ROS; SD; UDS; benzo-[a]-pyrene; carbadox; chromosomal aberration; ethylmethanesulfonate; hypoxanthine aminopterin thymidine; micronucleus; mitomycin C; newborn calf serum; olaquindox; quinocetone; quinoxaline 1,4-dioxides; reactive oxygen species; standard deviation; unscheduled DNA synthesis