Studies have demonstrated that the induction of oxidative stress may be involved in
brain tumor induction in rats by
acrylonitrile. The present study examined whether
acrylonitrile induces oxidative stress and DNA damage in rats and whether blood can serve as a valid surrogate for the biomonitoring of oxidative stress induced by
acrylonitrile in the exposed population. Male Sprague-Dawley rats were treated with 0, 3, 30, 100, and 200 ppm
acrylonitrile in
drinking water for 28 days. One group of rats were also coadministered N-acetyl
cysteine (NAC) (0.3% in diet) with
acrylonitrile (200 ppm in
drinking water) to examine whether
antioxidant supplementation was protective against
acrylonitrile-induced oxidative stress. Direct
DNA strand breakage in white blood cells (WBC) and brain was measured using the alkaline comet assay. Oxidative DNA damage in WBC and brain was evaluated using
formamidopyrimidine DNA glycosylase (fpg)-modified comet assay and with high-performance liquid chromatography-electrochemical detection. No significant increase in direct
DNA strand breaks was observed in brain and WBC from
acrylonitrile-treated rats. However, oxidative DNA damage (fpg comet and 8'
hydroxyl-2-
deoxyguanosine) in brain and WBC was increased in a dose-dependent manner. In addition, plasma levels of
reactive oxygen species (ROS) increased in rats administered
acrylonitrile. Dietary supplementation with NAC prevented
acrylonitrile-induced oxidative DNA damage in brain and WBC. A slight, but significant, decrease in the GSH:
GSSG ratio was seen in brain at
acrylonitrile doses > 30 ppm. These results provide additional support that the mode of action for
acrylonitrile-induced
astrocytomas involves the induction of oxidative stress and damage. Significant associations were seen between oxidative DNA damage in WBC and brain, ROS formation in plasma, and the reported
tumor incidences. Since oxidative DNA damage in brain correlated with oxidative damage in WBC, these results suggest that monitoring WBC DNA damage maybe a useful tool to assess
acrylonitrile-induced oxidative stress in humans.