Abstract: Sentinel Cells, respond quickly and differentially to and among various high explosives (e.g., RDX, PETN, HMX, TNT, TNG), taggant (DMDNB), and bacteria, as well as volatiles of commercial C4, Semtex 1A, and military C4. These effects are observable within 5 minutes of exposure, indicate profound biological effects in exposed cells, and are distinctly different from responses to bacteria (e.g., E. coli, mycoplasma, lipopolysaccharide from E. coli, etc.). Quantitative and mechanistic analysis of the observations indicate that the mechanisms that give rise to these responses invoke different subsets of biochemical reactions. The mechanism within the exposed Sentinel Cells is also used in canine olfactory cells (e.g., bomb dogs). The nature of the explosives-induced biological effects provide for a cell based explosives detection system (i.e., a cellular dog nose), as well as a tool for the study of biological effects of energetic materials on humans.