Profiling molecular changes in N,N-Dimethyl-p-toluidine-induced nasal cavity toxicity

Authors

• JK Dunnick
• BA Merrick
• G Flake
• J Foley
• A Brix
• K Gerrish
• KR Shockley

Abstract

N,N-Dimethyl-p-toluidine (DMPT) (Cas No. 99-97-8), an accelerator for methyl methacrylate monomers in medical devices, is a nasal cavity carcinogen in 2-year cancer studies in male and female F344/N rats, and is thought to cause its toxic effects in part due to oxidative damage. In this study we exposed rats for five days to DMPT (0 and 120 mg/kg), harvested nasal cavity transitional cell epithelium, and analyzed nasal gene transcript expression patterns to profile early molecular changes. Nanostring technology confirmed microarray findings of selected genes. DMPT transitional cell epithelium gene transcript patterns were characteristic of an anti-oxidative damage response (e.g.AKR7A3, MAFF, MGST3), cell proliferation, decrease in apoptotic function, and overlapped gene patterns found in head and neck cancers. Amino acid transporters were upregulated (e. g, SLC7A11). The DMPT nasal transcript pattern was similar to that found in the nasal cavity of the rat after 13-weeks of formaldehyde exposure with over 1000 transcripts in common. Cancer is a multistep process, and the early molecular changes in the nasal cavity after DMPT exposure are candidate markers for nasal cavity environmental toxins.

Scientific Focus Area: Cancer Biology

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