Ochratoxin A induces DNA damage and G2 phase arrest in human esophageal epithelium Het-1A cells in vitro.
Ochratoxin A (OTA), a toxin produced by several species of Aspergillus and Penicillium, is one of the most abundant food-contaminating mycotoxins. The International Agency for Research on Cancer (IARC) has classified OTA as a possible human carcinogen. Our previous study showed that there were high levels of OTA contaminations in wheat in the areas with high incidence of esophageal cancer in north China. This finding suggests that exposure to low levels of OTA may be a critical etiological factor for esophageal cancer in these areas. However, up to now, the potential biological effects of OTA on human esophageal epithelial cells have not been fully elucidated. In the present study, we explored the cytotoxicity of OTA in human esophageal epithelium immortalized cells (Het-1A). We found that OTA could induce DNA strand breaks and chromosome aberrations in Het-1A cells. OTA-induced DNA damage was followed by G2 cell cycle arrest, and down-regulation of Cdc2 and cyclinB1 contributed to the OTA-induced G2 arrest in Het-1A cells. Additionally, OTA induced apoptosis in Het-1A cells by activating caspase-3. In conclusion, our results indicated that OTA could induce DNA damage, G2 arrest and apoptosis in Het-1A cells, which may be involved in the esophageal toxicity of OTA.
Department of Pathology, General Hospital of Chinese People's Armed Police Force, China.
Jing
J
Liu
Sha
S
Wu
Haitao
H
Shen
Jinfeng
J
Cui
Yuan
Y
Wang
Lingxiao
L
Xing
Junling
J
Wang
Xia
X
Yan
Xianghong
X
Zhang
D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase; D002273:Carcinogens; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000187:drug effects; D056744:Cyclin B1 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D004947:Esophagus / Q000166:cytology* / Q000187:drug effects*; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D009793:Ochratoxins / Q000633:toxicity*
C534699:CCNB1 protein, human; D002273:Carcinogens; D056744:Cyclin B1; D009793:Ochratoxins; C025589:ochratoxin A; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D053148:Caspase 3