ABSTRACT
Potential genotoxic effects of diffusion flame-derived particulate matters (PMs), known to cause various adverse health problems, doped with iron, one of the representative heavy metals frequently found in the atmosphere, were examined. B6C3F1 mice were exposed to PMs [chamber 1 (low), 100; chamber 2 (middle), 200; and chamber 3 (high), 400 microg/m3] for 6 h/day, 5 days/week for one, two and four weeks in 1.5 m3 whole-body inhalation chambers. Our diffusion flame system produced 94.8 and 5.2% fine PM2.5 and PM10, respectively, with 89% of PM2.5 sized between 0.1 and 0.2 microm. Two cytogenetic endpoints were investigated through chromosomal aberration and supravital micronucleus (SMN) assays. Frequencies of cells with chromosome aberration (%) were observed in time- and concentration-dependent manners except in one-week exposure group, as also observed in SMN study. Generally, noniron flame induced less chromosome aberration than iron-doped flame, an indication that iron particles could potentiate urban PM toxicity. The above results indicate our diffusion flame system generated genotoxic fine PMs, whose effects were potentiated by organometallic particles such as iron. Our system can provide reliable PM models for studying the toxicity of urban fine PMs applicable for risk assessment.
Subject(s)
Air Pollutants/toxicity , Chromosome Aberrations/drug effects , Iron/toxicity , Mutagens/toxicity , Animals , Atmosphere Exposure Chambers , Female , Iron/administration & dosage , Male , Mice , Mutagens/administration & dosageABSTRACT
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.
Subject(s)
Carcinogens/toxicity , Dibutyl Phthalate/toxicity , Hypoxanthine Phosphoribosyltransferase/genetics , Mutation , Nitrosamines/toxicity , Ozone/toxicity , Animals , DNA Mutational Analysis , Drug Combinations , Female , Male , Mice , Mutagenicity Tests , Mutation/drug effects , Reverse Transcriptase Polymerase Chain Reaction , T-Lymphocytes/drug effects , T-Lymphocytes/enzymologyABSTRACT
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.
