Genotoxicity of quinocetone, cyadox and olaquindox in vitro and in vivo

Food Chem Toxicol. 2013 Sep:59:207-14. doi: 10.1016/j.fct.2013.06.008. Epub 2013 Jun 15.

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.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Infective Agents / administration & dosage
  • Anti-Infective Agents / toxicity*
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Cell Line
  • Cells, Cultured
  • Cricetinae
  • Cricetulus
  • DNA Replication / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Lymphocytes / cytology
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Male
  • Mice
  • Mice, Inbred Strains
  • Micronuclei, Chromosome-Defective / chemically induced
  • Mutagens / administration & dosage
  • Mutagens / toxicity*
  • Mutation / drug effects
  • Quinoxalines / administration & dosage
  • Quinoxalines / toxicity*
  • Random Allocation
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / growth & development
  • Salmonella typhimurium / metabolism

Substances

  • Anti-Infective Agents
  • Mutagens
  • Quinoxalines
  • quinocetone
  • cyadox
  • olaquindox