Dexamethasone ameliorates oxidative DNA damage induced by benzene and LPS in mouse bone marrow

Abstract

Mice were grouped to receive vehicle, dexamethasone (DEX), lipopolysaccharide (LPS), benzene (BZ, 200 mg/kg) and combinations: LPS + DEX, BZ + DEX, LPS + BZ, LPS + DEX + BZ. The DNA damage in bone marrow cells from BZ group was enhanced 2.8-fold measured by nuclear 8-hydroxy-2′-deoxyguanosine(8-oxodG) and 1.4-fold measured by Comet score (index of DNA breaks) (p<0.05). In the BZ + DEX group, 8-oxodG level and the Comet score were lowered to 65% and 76% respectively of that in the BZ group (p<0.05). The BZ + LPS caused a 3.9-fold increase in 8-oxodG and a 1.6-fold increase in the Comet score (p<0.05). The LPS + DEX + BZ lowered 8-oxodG level and the Comet score to 50% and 78% of the values in the LPS + BZ group, respectively (p<0.05). Nitrate/nitrite levels in serum were higher after BZ + LPS treatment than after all other treatments. Both 8-oxodG level and the Comet scores were correlated to the serum nitrate/nitrite level across all the treatments (r=0.55, p<0.01 and r=0.69, p<0.01, respectively). In bone marrow cells the 8-oxodG correlated with the Comet scores (r=0.80, p<0.01). We conclude that DEX administration can reduce the DNA damage from BZ treatment and from the combination of BZ and LPS. The correlation of DNA damage with nitrate/nitrite indicates the possible involvement of reactive nitrogen species (RNS) in the interaction between BZ and the inflammatory reaction stimulated by LPS. The 8-oxodG determination is more sensitive than strand break analysis by the Comet assay in bone marrow in vivo in mice for measuring the BZ-induced DNA damage.

Keywords:

• Benzene
• lipopolysaccharide (LPS)
• dexamethasone (DEX)
• 8-hydroxy-2′-deoxyguanosine (8-oxodG)
• single cell gel electrophoresis (Comet assay)
• reactive nitrogen species (RNS)