Résumé
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.
Sujets)
Animaux , Souris , Technique de Western , Protéines de liaison à l'ADN/métabolisme , Phtalate de dibutyle/toxicité , Test de retard de migration électrophorétique , Rein/effets des médicaments et des substances chimiques , Foie/effets des médicaments et des substances chimiques , Lignées consanguines de souris , Facteur-2 apparenté à NF-E2 , Facteur de transcription NF-kappa B/métabolisme , Nitrosamines/toxicité , Ostéopontine , Ozone/toxicité , Protéines proto-oncogènes/métabolisme , Appréciation des risques , Sialoglycoprotéines/métabolisme , Transactivateurs/métabolisme , Facteur de transcription AP-1/métabolismeRésumé
No abstract available.