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.
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.
Kim
Min Young
MY
Laboratory of Toxicology, College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Korea.
Kim
Hyun Woo
HW
Park
Jin Hong
JH
Kim
Jun Sung
JS
Jin
Hwa
H
Moon
Seo Hyun
SH
Eu
Kook Jong
KJ
Cho
Hyun Sun
HS
Kang
Gami
G
Kim
Yoon Shin
YS
Kim
Young Chul
YC
Kim
Hae Yeong
HY
Lee
Ki-Ho
KH
Cho
Myung Haing
MH
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
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