Patulin-induced genotoxicity and modulation of glutathione in HepG2 cells.
Patulin (PAT), a mycotoxin produced by certain species of Penicillium, Aspergillus and Byssochlamys, is mainly found in ripe apple and apple products. In our present study, a significant increase of the micronuclei frequency induced by PAT was found in human hepatoma HepG2 cells. To elucidate the role of glutathione (GSH) in the effect, the intracellular GSH level was modulated by pre-treatment with buthionine-(S, R)-sulfoximine (BSO), a specific GSH synthesis inhibitor, and by pre-treatment with N-acetylcysteine (NAC), a GSH precursor. It was found that depletion of GSH in HepG2 cells with BSO dramatically increased the PAT-induced micronuclei frequencies and that when the intracellular GSH content was elevated by NAC, the chromosome damage induced by PAT was significantly prevented in our test concentrations (0.19-0.75 microM). These results indicate that GSH play an important role in cellular defense against PAT-induced genotoxicity.
Zhou
Si-min
SM
Department of Toxicology, Dalian Medical University, No. 9, West Segment of South Ivshun Road, Dalian 116044, China.
Jiang
Li-ping
LP
Geng
Cheng-yan
CY
Cao
Jun
J
Zhong
Lai-fu
LF
D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage; D005978:Glutathione / Q000378:metabolism* / Q000502:physiology; D005981:Glutathione Synthase / Q000037:antagonists & inhibitors; D006801:Humans; D048629:Micronuclei, Chromosome-Defective; D010365:Patulin / Q000633:toxicity*
D010365:Patulin; D005981:Glutathione Synthase; D005978:Glutathione