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.
- Author:
Min Young KIM
;
Kyung Suk SONG
;
Gun Ho PARK
;
Seung Hee CHANG
;
Hyun Woo KIM
;
Jin Hong PARK
;
Hwa JIN
;
Kook Jong EU
;
Hyun Sun CHO
;
Gami KANG
;
Young Chul KIM
;
Myung Haing CHO
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
dibutyl phthalate (DBP);
inhalation;
mixture toxocity;
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK);
Ozone
- MeSH:
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
- From:Journal of Veterinary Science
2004;5(2):131-137
- CountryRepublic of Korea
- Language:English
-
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.
