[Study on genetic toxicity of gaseous benzene to mouse bone marrow cells]

To investigate the mechanism of genetic toxicity of gaseous benzene to mouse bone marrow cells and to provide an experimental basis for the discovery of early biomarkers among benzene-exposed population.

Male mice were randomly divided into control group and three benzene-exposed groups (6 mice per group). The control group was exposed to ambient air, and the three benzene-exposed groups were exposed to different concentrations of benzene (400, 800, and 1 600 mg/m(3)) for 15 days, 2 hours per day, in static inhalation chambers. At the end of the 15-day experimental period, the mice were killed. Bone marrow cells were separated from sacrificed mice, and superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) activity, myeloperoxidase (MPO) activity, and malondialdehyde (MDA) content were determined by biochemical methods. DNA damage was evaluated by micronucleus assay and single cell gel electrophoresis (SCGE). The expression of MPO protein was determined by immunocytochemistry.

The SOD activities in different dose groups (88.67 ± 13.58, 73.64 ± 4.50, and 67.63 ± 5.42 U/mg prot) were significantly decreased as compared with the control group (119.98±9.42 U/mg prot) (P<0.01). Moreover, the SOD activities in medium- and high-dose groups were significantly lower than that of the low-dose group (P < 0.05). The GSH-Px activities in medium- and high-dose groups (705.07 ± 93.75 and 674.77 ± 86.80 U/mg prot) were significantly decreased as compared with that of the control group (940.25 ± 82.63 U/mg prot) (P < 0.01), and the high-dose group had a significantly lower GSH-Px activity than the low-dose group (674.77 ± 86.80 U/mg prot vs 833.98 ± 130.64 U/mg prot, P < 0.05). The MDA content of low-, medium-, and high-dose groups (22.42±2.67, 22.38±3.02, and 27.66±2.89 nmol/mg prot) were significantly higher than that of the control group (12.35±1.58 nmol/mg prot) (P < 0.01), and MDA content was significantly higher in the high-dose group than in the medium- and low-dose groups (P < 0.05). The micronucleus assay showed that the micronucleus rates in different dose groups (4.67±0.82‰, 5.00±0.89‰, and 5.33±1.03‰) were significantly higher than that of the control group (2.50±0.55‰) (P < 0.01). The SCGE demonstrated that the DNA damage rates of medium- and high-dose groups (22.08% and 25.68%) were significantly higher than that of the control group (7.00%) (P < 0.01), and the DNA damage rate of high-dose group was significantly higher than that of the low-dose group (11.24%) (P < 0.05). MPO activity increased with the dose of benzene in all three benzene-treated groups (16.79±2.16, 19.46±2.28, and 22.53±2.76 U/g prot) and was significantly higher than that of the control group (12.89±0.74 U/g prot) (P < 0.01). The positive rates of MPO protein expression in low-, medium-, and high-dose groups (13.20±2.28%, 30.80±3.35%, and 40.20±1.92%) were significantly higher than that of the control group (6.60±1.14%) (P < 0.01). The MPO activity in high-dose group and the positive rates of MPO protein expression in medium- and high-dose groups were all significantly higher than those of the low-dose group (P < 0.01).

Gaseous benzene exposure has toxic effect on genetics of mouse bone marrow cells. It leads to chromosome breakage and DNA damage, enhances the activity and protein expression of MPO, and induces lipid peroxidation. Lipid peroxidation damage is a potential mechanism by which gaseous benzene exerts toxic effect on mouse bone marrow cells.