RESUMO
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.
Assuntos
Animais , Camundongos , Western Blotting , Proteínas de Ligação a DNA/metabolismo , Dibutilftalato/toxicidade , Ensaio de Desvio de Mobilidade Eletroforética , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Camundongos Endogâmicos , Fator 2 Relacionado a NF-E2 , NF-kappa B/metabolismo , Nitrosaminas/toxicidade , Osteopontina , Ozônio/toxicidade , Proteínas Proto-Oncogênicas/metabolismo , Medição de Risco , Sialoglicoproteínas/metabolismo , Transativadores/metabolismo , Fator de Transcrição AP-1/metabolismoRESUMO
No abstract available.