Molecular mechanism of mutagenesis induced by olaquindox using a shuttle vector pSP189/mammalian cell system.
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.
Hao
Lihua
L
Division of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Beijing 100094, PR China.
Chen
Qian
Q
Xiao
Xilong
X
D000818:Animals; D001483:Base Sequence; D002522:Chlorocebus aethiops; D004247:DNA / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D005822:Genetic Vectors; D006133:Growth Substances / Q000633:toxicity; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000187:drug effects*; D009153:Mutagens / Q000633:toxicity*; D010957:Plasmids / Q000235:genetics; D011810:Quinoxalines / Q000633:toxicity*; D014162:Transfection; D014709:Vero Cells
D006133:Growth Substances; D009153:Mutagens; D011810:Quinoxalines; D004247:DNA; C013168:olaquindox