J Vet Sci.
2004 Dec;5(4):379-385.
Molecular analysis of hprt mutation in B6C3F1 mice exposed to ozone alone and combined treatment of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone and/or dibutyl phthalate for 32 and 52 weeks
- Affiliations
-
- 1Laboratory of Toxicology, College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Korea. mchotox@snu.ac.kr
- 2Institute of Environmental & Industrial Medicine, Hanyang University, Seoul 133-791, Korea.
- 3Department of Public Health, College of Natural Science, Keimyung University, Daegu 705-751, Korea.
- 4Department of Food Science, School of Biotechnology,and College of Industry, KyungHee University, Suwon 449-701, Korea.
- 5Laboratory of Molecular Cancer Biology, Korea Cancer Center Hospital, Seoul 139-706, Korea.
Abstract
- Potential toxicological interactions of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and/or dibuthyl phthalate (DBP) on ozone were investigated after 32- and 52-wk exposures using hprt mutation assay. Male and female B6C3F1 mice exposed to ozone (0.5 ppm), NNK (1.0 mg/kg), DBP (5,000 ppm), and two or three combinations of these toxicants 6 h per day for 32- and 52-wk showed increases in the frequencies of TG rlymphocytes compared to the control groups. Additive interactions were noted from two combination groups compared to the ozone alone in both sexes of 32- and 52-wk studies. The most common specific mutation type in the hprt genes of test materials-treated male and female mice was transversion with very few transition. The results indicate that such dominant transversion may be responsible for toxicity and combined exposure to ozone, NNK, and DBP induces additive genotoxicities compared to ozone alone.
Keyword
- Ozone; NNK; DBP; hprt mutation
MeSH Terms
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Animals
Carcinogens/*toxicity
DNA Mutational Analysis
Dibutyl Phthalate/*toxicity
Drug Combinations
Female
Hypoxanthine Phosphoribosyltransferase/*genetics
Male
Mice
Mutagenicity Tests
*Mutation/drug effects
Nitrosamines/*toxicity
Ozone/*toxicity
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes/drug effects/enzymology
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