title: 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.
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.
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Korea.
authors.forename: Min Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Kim
authors.forename: Jin Hong
authors.initials: JH
authors.lastname: Park
authors.forename: Jun Sung
authors.initials: JS
authors.lastname: Kim
authors.forename: Hwa
authors.initials: H
authors.lastname: Jin
authors.forename: Seo Hyun
authors.initials: SH
authors.lastname: Moon
authors.forename: Kook Jong
authors.initials: KJ
authors.lastname: Eu
authors.forename: Hyun Sun
authors.initials: HS
authors.lastname: Cho
authors.forename: Gami
authors.initials: G
authors.lastname: Kang
authors.forename: Yoon Shin
authors.initials: YS
authors.lastname: Kim
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Hae Yeong
authors.initials: HY
authors.lastname: Kim
authors.forename: Ki-Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Myung Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004252:DNA Mutational Analysis; D003993:Dibutyl Phthalate / Q000633:toxicity*; D004338:Drug Combinations; D005260:Female; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects; D009602:Nitrosamines / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology
chemical_list: D002273:Carcinogens; D004338:Drug Combinations; D009602:Nitrosamines; D003993:Dibutyl Phthalate; D010126:Ozone; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D007041:Hypoxanthine Phosphoribosyltransferase