Genotoxicity evaluation of Mequindox in different short-term tests

Food Chem Toxicol. 2013 Jan:51:330-6. doi: 10.1016/j.fct.2012.10.003. Epub 2012 Oct 12.

Abstract

Quinoxaline-1,4-dioxides (QdNOs) are the potent heterocyclic N-oxides with interesting biological properties such as antibacterial, anticandida, antitubercular, anticancer and antiprotozoal activities. Here, we tested and compared the mequindox (MEQ) for mutagenic abilities in a battery of different short term tests according to OECD guidelines. When compared with the controls, a strong mutagenicity of MEQ and carbadox (CBX) was observed with an approximate concentration-effect relationship in Salmonella reverse mutation test, chromosome aberration test, unscheduled DNA synthesis assay and HGPRT gene mutation test, in the absence and presence of S(9)-mix. In in vivo micronucleus test, CBX produced significant increase in the proportion of micronucleus formation than MEQ in mice bone marrow cells. From these results, we can conclude that MEQ had a strong genotoxic potential to mammalian cells in vitro as well as in vivo and its mutagenicity is slightly higher than CBX. Our results, for the 1st time, discuss the genotoxic potential of MEQ. These results not only confirm the earlier findings about CBX but also extend the knowledge and awareness about the genotoxic risk of QdNO derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / drug effects
  • Carbadox / toxicity
  • Chromosome Aberrations
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Humans
  • Hypoxanthine Phosphoribosyltransferase / genetics
  • Lymphocytes / drug effects
  • Male
  • Mice
  • Micronucleus Tests
  • Mutagenicity Tests / methods*
  • Quinoxalines / toxicity*
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics

Substances

  • Mequindox
  • Quinoxalines
  • Hypoxanthine Phosphoribosyltransferase
  • Carbadox