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Deoxidation rates play critical role in DNA damage of important synthetic drugs, quinoxaline 1,4-dioxides Xu Wang, Huahai Zhang, Lingli Huang, Yuanhu Pan, Juan Li, Dongmei Chen, Guyue Cheng, Haihong Hao, Yanfei Tao, Zhenli Liu, and Zonghui Yuan Chem. Res. Toxicol., Just Accepted Manuscript • Publication Date (Web): 27 Jan 2015 Downloaded from http://pubs.acs.org on January 29, 2015
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Chemical Research in Toxicology
Deoxidation rates play critical role in DNA damage of important synthetic drugs, quinoxaline 1,4-dioxides
Xu Wang †┴, Huahai Zhang ‡┴, Lingli Huang †, Yuanhu Pan §, Juan Li §, Dongmei Chen , Guyue Cheng §, Haihong Hao ║, Yanfei Tao ║, Zhenli Liu ║, Zonghui Yuan †,§, ║*
§
†
National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, §MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong
Agricultural University, ║Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, Hubei 430070, China.
‡
College of Forestry, Northwest A&F University, Yangling, Shaanxi 712100, China
┴
These authors contribute equally to this paper
*Corresponding author: Prof. Dr. Zonghui Yuan, Tel: 0086-27-87287186， Fax: 0086-27-87672232，E-mail address:
[email protected] TITLE RUNNING HEAD: Deoxidation Rates Control DNA Damage of QdNOs.
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Chemical Research in Toxicology
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Chemical Research in Toxicology
Abstract Quinoxaline 1,4-dioxides (QdNOs) are synthetic agents with the wide range of biological activities. However, DNA damage of QdNOs is far from clear. Five classical members of QdNOs, quinocetone (QCT), mequindox (MEQ), carbadox (CBX), olaquindox (OLA) and cyadox (CYA) were used to investigate the genotoxicity of QdNOs. The deoxidation rate of QdNOs was presumed to play roles in their genotoxicity. Deoxidation rates of QdNOs in both rat and pig liver microsomes were investigated by using LC/MS-IT/TOF, and their relative quantifications were achieved with HPLC. To reveal the relationships between the deoxidation rates and the genotoxicity, the parameters of cell damage, oxidative stress and DNA damage were detected. Under low oxygen condition, the rank orders of the desoxy-rates
and
bidesoxy-rates
in
rat
and
pig
liver
microsomes
were
QCT
