Increased gene expression in human promyeloid leukemia cells exposed to trans,trans-muconaldehyde, a hematotoxic benzene metabolite.

摘要: The hematotoxicity of benzene, a human leukemogen, has been postulated to be mediated by reactive metabolites and involve cell damage caused oxygen species. Because expression the transcription factors AP-1 NF-kappaB is sensitive redox state in eukaryotic cells, DNA binding activity was examined HL-60 promyeloid leukemia cells exposed trans,trans-muconaldehyde, microsomal hematotoxic metabolite benzene. There little nuclear extracts from control based on electrophoretic mobility shift assays. Exposure 0.1 microM MUC for 4 h resulted significantly increased levels protein with high sequence specificity consensus sequence. In addition, assays showed strong increase factor site. latter highest treated 1.0 muconaldehyde cultured h. an c-fos c-jun mRNA levels. Western blot analysis that 1 4-6 subsequently decreased gradually. Increased observed bone marrow B6C3F1 mice 2 after administration 440 mg/kg We suggest gene up-regulation may play role mechanism benzene leukemogenesis.