Investigation of quinocetone-induced genotoxicity in HepG2 cells using the comet assay, cytokinesis-block micronucleus test and RAPD analysis.
Quinocetone, a new quinoxaline 1,4-dioxide derivative, has been approved as an animal growth promoter in China since 2003. To investigate the genotoxicity of quinocetone in vitro, its effects on the extent of DNA injury in human hepatoma (HepG2) cells accompanied by chromosomal damage and genomic DNA alterations were tested. The cell viability test indicated that quinocetone inhibited cell proliferation as a function of dose and time. In the comet assay, significant DNA fragment migration was observed in a dose-dependent manner. A dose-dependent increase of the micronucleated (MN) cell frequency was shown in cytokinesis-block micronucleus (CBMN) test. The gain/loss of randomly amplified polymorphic DNA (RAPD) bands and the change of band intensity in RAPD profiles were obtained after HepG2 cells were exposed to quinocetone at concentrations of 1.25, 2.5 and 5 microg/mL. The results demonstrated that quinocetone exerted genotoxic effects on HepG2 cells. Thus, the use of quinocetone as a growth promoter in animal feed should be seriously considered.
Jin
Xi
X
Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.
Chen
Qian
Q
Tang
Shu-Sheng
SS
Zou
Jia-Jie
JJ
Chen
Kai-Pao
KP
Zhang
Ting
T
Xiao
Xi-Long
XL
D045744:Cell Line, Tumor; D048750:Cell Nucleus Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D048749:Cytokinesis / Q000187:drug effects; D004249:DNA Damage; D006801:Humans; D015162:Micronucleus Tests; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D011810:Quinoxalines / Q000737:chemistry / Q000633:toxicity*; D019105:Random Amplified Polymorphic DNA Technique
D009153:Mutagens; D011810:Quinoxalines; C502851:quinocetone