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Inducible and Reversible Dominant-negative DN Protein Inhibition
Published on: January 7, 2019
Expression of multidrug resistance 1 and multidrug resistance-related protein 1 in C57BL/6 mice treated with benzene
1Department of Occupational Disease, Jinshan Hospital, Fudan University, Shanghai, China.
Abstract:
ATP-binding cassette super family (ABC) proteins are considered key to oncology and pharmacology studies. We examined the effect of benzene on ABC pump protein levels in C57BL/6 mouse bone marrow mononuclear cells. After a 2-week gavage (200 mg/kg, 5 days per week), the number of peripheral leukocytes, lymphocytes and basophils dropped significantly; there was also a significant decrease in MDR1 and MRP1 gene expression. A significant reduction in expression of P-gp was found; however, there was no significant decrease in the expression of MRP1 and NF-κB p65. We conclude that regulation of membrane efflux transport protein could be a factor in benzene hematotoxicity.
Insights
Benzene exposure significantly reduced white blood cell counts and key drug efflux pump gene expression, including P-glycoprotein (P-gp), in mouse bone marrow. This suggests altered membrane transport proteins contribute to benzene
Area of Science:
- Biochemistry
- Toxicology
- Pharmacology
Background:
- ATP-binding cassette (ABC) super family proteins are crucial in oncology and pharmacology.
- ABC transporters play vital roles in cellular detoxification and drug resistance.
Purpose of the Study:
- To investigate the impact of benzene exposure on ABC transporter protein levels.
- To determine the relationship between benzene hematotoxicity and ABC pump expression in mouse bone marrow.
Main Methods:
- C57BL/6 mice were administered benzene via gavage (200 mg/kg, 5 days/week for 2 weeks).
- Peripheral blood cell counts (leukocytes, lymphocytes, basophils) were analyzed.
- Gene expression levels of MDR1, MRP1, and NF-κB p65 were quantified.
- Protein expression of P-glycoprotein (P-gp) was assessed.
Main Results:
- Benzene exposure led to significant decreases in peripheral leukocytes, lymphocytes, and basophils.
- A significant reduction in MDR1 and MRP1 gene expression was observed.
- P-glycoprotein (P-gp) expression was significantly decreased.
- No significant changes were found in MRP1 protein or NF-κB p65 expression.
Conclusions:
- Benzene exposure induces hematotoxicity in mice.
- Downregulation of membrane efflux transport proteins, such as P-gp, may contribute to benzene-induced bone marrow toxicity.
- Further research into ABC transporter regulation is warranted for understanding benzene toxicity.
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