Selenite induces oxidative DNA damage in primary rat hepatocyte cultures

Abstract

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 10μmol/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 10μmol/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 10μmol/L. Furthermore, an increase in 8-hydroxydeoxyguanosine induced by selenite ions (10μmol/L) was inhibited by free radical scavengers (α-tocopherol, N-acetyl-l-cysteine, and melatonin) at concentrations more than 50μmol/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.