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 mu mol/L (16-, 25- and 36-fold). Selenite ions also induced DNA fragmentation in nucleus from the hepatocyte cultures at concentrations of 5 and 10 mu mol/L Selenite ions could not affect protein expression levels of 8-oxoguanine DNA glycosylase I 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 mu mol/L Furthermore, an increase in 8-hydroxydeoxyguanosine induced by selenite ions (10 mu mol/L) was inhibited by free radical scavengers (alpha-tocopherol, N-acetyl-L-Cysteine, and melatonin)at concentrations more than 50 mu mol/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 I protein expression levels (C) 2009 Elsevier Ireland Ltd. All rights reserved