Combined treatment with 4-(N-methyl-N-nitrosamino)-1- (3-pyridyl)-1-butanone and dibutyl phthalate enhances ozone-induced genotoxicity in B6C3F1 mice.
Potential toxicological interactions of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and/or dibutyl phthalate (DBP) with ozone were investigated. Male and female B6C3F1 mice were exposed to ozone (0.5 p.p.m.), NNK (1.0 mg/kg), DBP (5000 p.p.m.) and different combinations of these toxicants 6 h/day for 16, 32 and 52 weeks. Two cytogenetic end-points, determined by the chromosomal aberration (CA) and supravital micronucleus (SMN) assays, were investigated in vivo. Our results show that all treated groups of both sexes showed genotoxic effects when compared with the control group. Additive and/or synergistic responses were observed in the CA assay for all test periods when mice of both sexes were exposed to ozone and NNK, ozone and DBP and the combination of ozone, NNK and DBP. In the SMN assay, additive interactions were noted for both sexes in the 16 and 32 week studies, similar to the results with the CA assay. All combination groups of both sexes showed synergistic interactions in the 52 week study. The results indicate that combined exposure to ozone, NNK and DBP in both sexes of mice has enhanced genotoxic effects compared with exposure to ozone alone.
Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Suwon 441-744, Korea. mchotox@snu.ac.kr
Min Young
MY
Kim
Yong Chul
YC
Kim
Myung Haing
MH
Cho
D000818:Animals; D001769:Blood / Q000187:drug effects; D002869:Chromosome Aberrations; D003993:Dibutyl Phthalate / Q000633:toxicity*; D004357:Drug Synergism; D005260:Female; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015162:Micronucleus Tests; D009602:Nitrosamines / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D013154:Spleen / Q000166:cytology / Q000187:drug effects
D009602:Nitrosamines; D003993:Dibutyl Phthalate; D010126:Ozone; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone