Molecular mechanism of mutagenesis induced by olaquindox using a shuttle vector pSP189/mammalian cell system

Mutation Research
Lihua HaoXi-Long Xiao

Abstract

Olaquindox, a quinoxaline 1,4-dioxide derivative from quindoxin, is widely used as an animal growth promoter in China. We tested olaquindox as a mutagen in a SV40-based shuttle vector pSP189 and African green kidney cell (Vero E6 cell line) system to define the safety of olaquindox as a food-additive for animals. When applied at 6.6 microg/ml, olaquindox caused 12 times higher mutation frequency in comparison to untreated controls. More than 70% of base substitutions happened at G:C base pairs featuring G:C to T:A or G:C to A:T conversions. Frequency of point mutations for in vitro modified plasmids was also dramatically increased from the spontaneous background level. Olaquindox-induced mutations did not occur randomly along the supF shuttle vector, but instead, had a hot spot at base pair #155 which accounts for 37% of total mutations. Olaquindox-induced mutations also showed sequence-specificity in which most point mutations occurred at site N in a 5'-NNTTNN-3' sequence while most tandem bases deletion and rearrangement were seen at the 5'-ANGGCCNAAA-3' sequence. We conclude that olaquindox induces DNA mutation, therefore, should not be used as an additive to promote animal growth.

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Citations

Mar 31, 2012·Research in Veterinary Science·Guanghui LiZhenling Zeng
Aug 12, 2009·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Xi JinXi-Long Xiao
Dec 9, 2008·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Qian ChenXilong Xiao
Apr 25, 2012·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Tianci XuHongjing Jin
Dec 7, 2010·Regulatory Toxicology and Pharmacology : RTP·Xu WangZong-Hui Yuan
Jan 18, 2012·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Xu WangZong-Hui Yuan
May 14, 2016·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Qianying LiuZonghui Yuan
Apr 8, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Daowen LiShusheng Tang
Jan 19, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Daowen LiShusheng Tang
Nov 25, 2015·Toxicology Research·Xu WangZonghui Yuan
May 21, 2011·Molecular and Cellular Biochemistry·Ting ZhangXi-Long Xiao
Oct 12, 2017·Frontiers in Pharmacology·Qianying LiuZonghui Yuan
Sep 9, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Daowen LiShusheng Tang
Jun 11, 2020·Ecotoxicology and Environmental Safety·Yu-Qing GaoCheng-Guang Liang

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