Induction effect of benzene on apoptosis of mouse bone marrow cells through mitochondrial-dependent apoptosis pathway and its mechanism / 吉林大学学报(医学版)

ABSTRACT

Objective To establish mouse poisoning model by inhaling benzene, and to investigate the induction effect of benzene on the apoptosis of mouse bone marrow cells and its mechanism, and to provide an experimental basis for study on bone marrow toxicity mechanism.Methods 24 male mice were randomly divided into four groups (n=6).The mice in one group were exposed to ambient air (control group)and the mice in the other three groups were exposed to different doses (400,800,1 600 mg·m-3 )of benzene (low,middle and high doses of benzene groups)for 1 5 d in the respective inhalation chambers. At the end of the experiment, the mice were killed. The bone marrow of the mice was obtained. The pathological changes of the bone marrow cells of the mice in various groups were observed under light microscope with HE staining.The apoptotic rates and mitochondrial membrane potential (MMP ) of the mice in various groups were detected by flow cytometry, and the expressions of mitochondrial-deperdent apoptosis related gene proteins were determined with immunohistochemistry method. Results The number of distal and central cells in different doses of benzene groups were significantly reduced,and accompanied by blood sinus expansion in high dose of benzene group.The apoptotic rates of the cells in middle and high doses of benzene groups were obviously higher than that in control group (Ρ<0.01),and there were also significant differences between high dose group and low,middle doses of benzene groups (Ρ<0.05).The MMP was significantly decreased with the increasing of benzene doses, and there were significant differences between middle,high doses of benzene groups and control group (Ρ<0.05).The number of Bax,CytC positive cells in different doses of benzene groups and the number of Caspase-9,Caspase-3 positive cells in middle and high doses of benzene groups were significantly increased compared with control group(Ρ<0.05);the number of Bcl-2 positive cells in different doses of benzene groups was decreased(Ρ<0.05),and number of Bcl-2 positive cells in middle and high doses of benzene groups was decreased compared with low dose of benzene group (P<0.05). Conclusion Benzene with certain dose can induce the apoptosis of mouse bone marrow cells, and promote the expressions of mitochondrial apoptosis related gene proteins. Benzene-induced apoptosis through mitochondrial-dependent apoptosis pathway may be an important mechanism of bone marrow toxicity induced by benzene.