Mutagenic properties of dimethylaniline isomers in mice as evaluated by comet, micronucleus and transgenic mutation assays

Abstract

BackgroundThe carcinogenic potential of dimethylaniline (DMA) isomers in rodents and humans has been previously reported, and there is sufficient evidence for the carcinogenicity of 2,6-DMA in experimental animals. The target organ of carcinogenesis of 2,6-DMA is the nasal cavity. In the current study, six DMA isomers, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- and 3,5-DMA, were evaluated for mutagenic properties.ResultsMale ddY mice (3/group) were treated intragastrically (i.g.) with 200 mg/kg of one of the six DMAs, and a comet assay was performed on samples of bone marrow, kidney, liver and lung at 3 and 24 h after the treatment. Positive responses were observed in the kidney, liver and lungs of mice from all of the DMA treatment groups after 3 h and in the bone marrow of mice treated with either 3,4- or 3,5-DMA after 3 h; however, these effects were diminished at the 24 h time point. The micronucleus induction in the bone marrow was analysed in the same mouse at 24 h after the treatment. No induction of micronucleated polychromatic erythrocytes was observed after treatment with any of the DMAs.Male transgenic Muta™ mice (five/group) were treated i.g. with 2,5-, 2,6- or 3,5-DMA at 100 mg/kg bw weekly for 4 weeks, and the lacZ and the cII mutation frequencies were examined in the nasal cavity, liver and bone marrow at 7 days after the last treatment. Statistically significant increases in the mutation frequencies of the lacZ and/or cII genes were observed in the nasal cavity of 2,5-DMA or 2,6-DMA treated mice. Sequence analysis showed increased incidences of AT to GC and GC to TA mutations in the nasal tissues.ConclusionsThese findings suggest that the carcinogenic activities of DMAs are associated with mutagenic events.