Selenite induces oxidative DNA damage in primary rat hepatocyte cultures.
The effects of selenite ions on oxidative DNA damage in primary rat hepatocyte cultures were examined. Selenite ions dose-dependently stimulated 8-hydroxydeoxyguanosine formation in DNA from the hepatocyte cultures at concentrations of 1, 5 and 10 micromol/L (1.6-, 2.5- and 3.6-fold). Selenite ions also induced DNA fragmentation in nucleus from the hepatocyte cultures at concentrations of 5 and 10 micromol/L. Selenite ions could not affect protein expression levels of 8-oxoguanine DNA glycosylase 1 which is responsible for excision of 8-hydroxydeoxyguanosine from DNA, but could increase 2',7'-dichlorofluorescein-fluorescence intensity from 2',7'-dichlorodihydrofluorescein, an indicator of reactive oxygen species generation, at concentrations of 5 and 10 micromol/L. Furthermore, an increase in 8-hydroxydeoxyguanosine induced by selenite ions (10 micromol/L) was inhibited by free radical scavengers (alpha-tocopherol, N-acetyl-L-cysteine, and melatonin) at concentrations more than 50 micromol/L. These observations imply that selenite ions have the potential to induce oxidative DNA damage in the liver through an increase in reactive oxygen species formation, but not a decrease in 8-oxoguanine DNA glycosylase 1 protein expression levels.
Fujimoto
Yohko
Y
Laboratory of Physiological Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. fujimoto@gly.oups.ac.jp
Morinaga
Kazuhiro
K
Abe
Muneyuki
M
Kitamura
Takahiro
T
Sakuma
Satoru
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000737:chemistry; D004249:DNA Damage; D045647:DNA Glycosylases / Q000096:biosynthesis / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D005452:Fluoresceins; D005456:Fluorescent Dyes; D022781:Hepatocytes / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D018038:Sodium Selenite / Q000633:toxicity*
D005452:Fluoresceins; D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; C065013:2',7'-dichlorodihydrofluorescein; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D045647:DNA Glycosylases; C483741:OGG1 protein, rat; D003849:Deoxyguanosine; D018038:Sodium Selenite