DNA adducts from aromatic amines. Aromatic amines are pervasive in the environment (i.e. air, food, and water) and they originate from combustion of nitrogenous organic material and from synthetic organic materials that are fundamental to our economy (rubber, plastics, agricultural chemicals, drugs, dyes, etc). They constitute one of the most extensively studied classes of chemical carcinogens. A recent epidemiologic study of bladder cancer found that the arylamine, 3,5-dimethylaniline (3,5-DMA) may play a significant role in the etiology of this disease in non-smoking populations. One aim of this study is to identify the DNA adducts formed by 3,5-DMA in vitro in ct DNA and in vivo in gpt delta mice. The strategy will involve treatment of ctDNA with ¹⁴C-labeled 3,5-DMA activated by human or mice microsomes, isolation of adducts from DNA and characterization. The next step is administration of labeled compound to mice, isolation of adducts from DNA, and comparison to synthetic adducts standards guided by in vitro results. The other aim is to develop biomarkers of genotoxic metabolites based on urinary excretion products, especially covalent DNA adducts and products of glutathione conjugation. Click here to visit the BEAMS lab and learn more about accelerator mass spectrometry.
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