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

Mice were grouped to receive vehicle, dexamethasone (DEX), lipopolysacchari de (LPS), benzene (BZ, 200 mg/kg) and combinations: LPS + DEX, BZ + DEX, LP S + BZ, LPS + DEX + BZ. The DNA damage in bone marrow cells from BZ group w as enhanced 2.8-fold measured by nuclear 8-hydroxy-2'-deoxyguanosine (8-oxo dG) 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 cau sed a 3.9-fold increase in 8-oxodG and a 1.6-fold increase in the Comet sco re (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 tp < 0.05 ). Nitrate/nitrite levels in serum were higher after BZ + LPS treatment tha n 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 cell s the 8-oxodG correlated with the Comet scores (r = 0.80, p < 0.01). We con clude that DEX administration can reduce the DNA damage from BZ treatment a nd from the combination of BZ and LPS. The correlation of DNA damage with n itrate/nitrite indicates the possible involvement of reactive nitrogen spec ies (RNS) in the interaction between BZ and the inflammatory reaction stimu lated 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 t he BZ-induced DNA damage.