Quinocetone triggers oxidative stress and induces cytotoxicity and genotoxicity in human peripheral lymphocytes of both genders

Abstract

Quinocetone has been widely used as an animal growth promoter in China. However, available data showed that QCT has potential genotoxicity. This study was conducted to investigate the cytotoxicity and genotoxicity of QCT in human lymphocytes. CCK-8 assay demonstrated the severe inhibitory effects by QCT in a dose- and time-dependent manner. DNA damage analysis using alkalic Comet assay revealed a pronounced increase of DNA fragmentation in cells. In contrast, DNA damage was significantly decreased after incubation with S9 mix. This finding demonstrated that the intermediate metabolites of this drug exerted lower genotoxicity than its parent drugs. We further described chromosomal damage induced by this drug employing cytokinesis-block micronucleus assay. The micronucleus frequency was significantly increased in quinocetone groups as compared to controls. Similar to the observation in Comet assay, incorporation of S9 mix in the cytokinesis-block micronucleus assay could markedly alleviate the chromosomal damage. Moreover, QCT could invoke increase of reactive oxygen species generation in cells. Intriguingly, the toxicity of QCT was more prominent in samples from males than those from females under the same conditions. QCT could induce potential cytotoxicity and genotoxicity in human lymphocytes.