ABSTRACT
Toxic effects of ozone, 4-(N-methyl-N-nitrosamino)-1-(3- pyridyl)-1-butanone (NNK), and/or dibutyl phthalate (DBP) were examined through NF-kappaB, AP-1, Nrf2, and osteopontin (OPN) in lungs and livers of B6C3F1 mice. Electrophoretic mobility shift assay (EMSA) indicated that mice treated with combination of toxicants induced high NF-kappaB activities. Expression levels of p105, p65, and p50 proteins increased in all treated mice, whereas IkB activity was inhibited in NNK-, DBP-, and combination-treated ones. All treated mice except ozone-treated one showed high AP-1 binding activities. Expression levels of c-fos, c-jun, junB, jun D, Nrf2, and OPN proteins increased in all treated mice. Additive interactions were frequently noted from two-toxicant combination mice compared to ozone-treated one. These results indicate treatment of mixture of toxicants increased toxicity through NF-kappaB, AP-1, Nrf2, and OPN. Our data could be applied to the elucidation of mechanism as well as the risk assessment of mixture-induced toxicity.
Subject(s)
Animals , Mice , Blotting, Western , DNA-Binding Proteins/metabolism , Dibutyl Phthalate/toxicity , Electrophoretic Mobility Shift Assay , Kidney/drug effects , Liver/drug effects , Mice, Inbred Strains , NF-E2-Related Factor 2 , NF-kappa B/metabolism , Nitrosamines/toxicity , Osteopontin , Ozone/toxicity , Proto-Oncogene Proteins/metabolism , Risk Assessment , Sialoglycoproteins/metabolism , Trans-Activators/metabolism , Transcription Factor AP-1/metabolismABSTRACT
No abstract available.