The effects of benzene poisoning on expression of multidrug resistance 1 gene and P-glycoprotein in bone marrow mononuclear cells of C57BL/6 mice

Abstract

To investigate the effects of benzene poisoning on the expression of multidrug resistance 1 (MDR1) gene and P-glycoprotein (P-gp) in the bone marrow mononuclear cells (BMMNCs) of C57BL/6 mice. C57BL/6 mice were randomly divided into control group (n = 24), low-dose group (n = 24), medium-dose group (n = 24), and high-dose group (n = 24) to receive corn oil, 25 mg/kg benzene, 50 mg/kg benzene, or 100 mg/kg benzene by gavage, once daily, 5 days/weeks, for 4 weeks. The mice were sacrificed on day 12, 26, or 29 of poisoning. Peripheral blood routine test was performed; real-time quantitative PCR was used to measure the MDR1 gene expression in BMMNCs; Western blot was used to measure the P-gp expression in BMMNCs. On day 12, the red blood cell count and hemoglobin level in the high-dose group were significantly lower than those in the control group, low-dose group, and medium-dose group (P < 0.01 or P < 0.05). On day 26, the white blood cell count in the high-dose group was significantly lower than those in the control group, low-dose group, and medium-dose group (P < 0.01 or P < 0.05). At each time point, the mRNA expression of MDR1 gene in the low-dose group, medium-dose group, and high-dose group was significantly lower than that in the control group (P < 0.01). On day 26, the P-gp expression in the high-dose group was significantly lower than those in the control group, low-dose group, and medium-dose group, and the P-gp expression in the medium-dose group was significantly lower than that in the low-dose group (P < 0.01 or P < 0.05). On day 29, the P-gp expression in the low-dose group, medium-dose group, and high-dose group was significantly lower than that in the control group (P < 0.05). Benzene poisoning can affect the expression of MDR1 gene and P-gp, which may be one of the mechanisms of benzene hematotoxicity.