3,5-Dimethyaminophenol is not Mutagenic in Ames Test and HPRT Test and may have Anti-Carcinogenic Potential Against Lung Cancer Cells

Abstract

Exposure to 3,5-dimethylaminophenol (3,5-DMAP), the metabolite of the 3-5-dimethylaniline, was shown to cause high levels of oxidative stress in different cells. However, we have shown that this alkylaniline metabolite was non-mutagenic to different strains of Salmonella typhimurium in Ames test and also was found to be not mutagenic to CHO cells in HPRT test. Concerning all the available data, we aimed to observe whether this metabolite may have anti-carcinogenic potential in human non-small cell lung cancer line (A549 cells). 3,5-DMAP caused a dose-dependent increase in cytotoxicity and generation of superoxide (O2-.) and reactive oxygen species (ROS). 3,5-DMAP did not produce significant cytotoxicity to human lung fibroblasts even at very high concentrations; however showed higher cytotoxic effect on A549 lung cancer cells at the same concentrations. 3,5-DMAP also led to molecular events, like increases in apoptotic markers (i.e., p53, Bad, Bax and cytochrome and decreases anti-apoptotic proteins (Bcl-2). Furthermore, 3,5-DMAP provided significant decreases in cell viability of A549 cells and eventually inhibited growth of A549 cells in an in vivo mouse model. Tumor sections showed that 3,5-DMAP down-regulated c-Myc expression but up-regulated p53 and cytochrome c, all of which might result in tumor growth arrest. In conclusion, our findings demonstrate 3,5-DMAP is not mutagenic to Salmonella typhimurium and CHO cells; toxic to A549 cells and therefore may have anti-cancer properties, the importance of which should be elucidated with further mechanistic studies.

Keywords

• 3,5-dimethylaminophenol
• alkylaniline
• cytotoxicity
• apoptosis
• Ames test
• HGPRT test