J Vet Sci.  2004 Jun;5(2):131-137.

B6C3F1 mice exposed to ozone with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone and/or dibutyl phthalate showed toxicities through alterations of NF-kappaB, AP-1, Nrf2, and osteopontin

• Kim MY
• Song KS
• Park GH
• Chang SH
• Kim HW
• Park JH
• Jin H
• Eu KJ
• Cho HS
• Kang G
• Kim YC
• Cho MH

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.

Keyword

dibutyl phthalate (DBP); inhalation; mixture toxocity; 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK); Ozone

MeSH Terms

Animals
Blotting, Western
DNA-Binding Proteins/*metabolism
Dibutyl Phthalate/*toxicity
Electrophoretic Mobility Shift Assay
Kidney/*drug effects/metabolism
Liver/*drug effects/metabolism
Mice
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/metabolism