TOXI 87 |
| Substituted anilines are chemical intermediates used principally in the production of dyes, but may also occur in tobacco smoke and as degradation products of aniline-based pesticides. We have recently demonstrated high levels of hemoglobin adducts of 2,6-dimethylanliline (2,6-DMA), 3,5-dimethylaniline (3,5-DMA) and 3-ethylaniline (3-EA) in the blood of non-smokers. Although 2,6-DMA has been shown to be clearly carcinogenic for the nasal cavity of rats and mutagenic for S. typhimurium, little information is available on its mechanism of action or on the genotoxicity of 3,5-DMA and 3-EA. We are testing the hypothesis that their toxic effects are attributable to hydroxylamine and/or aminophenol metabolites. We have synthesized and evaluated the cytotoxicity and mutagenicity of N-hydroxy-2,6-DMA, N-hydroxy-3,5-DMA, N-hydroxy-3-EA, 2,6-dimethylaminophenol and 3,5-dimethylaminophenol in human lymphoblastoid TK6 and HCT116 colon cancer cells. All were cytotoxic to these cells, N-hydroxy-3-EA being the least potent; survival rates decreased linearly at doses in the range of 100-250uM for N-hydroxy derivatives of 2,6-DMA and 3,5-DMA. The latter were also found to be mutagenic in human lymphoblastoid TK6 cells, with N-hydroxy-3,5-DMA being more active than N-hydroxy-2,6-DMA. Additional studies are in progress. |
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Poster Presentations and Awards
6:00 PM-10:00 PM, Tuesday, 12 September 2006 Moscone Center -- Room 104, Poster
Sci-Mix
Division of Chemical Toxicology |