The cyclitol myo-inositol and its corresponding hexaphosphate (IP6) are promising agents for cancer prevention. Due to metabolic instability, the structure of the active compound or compounds and their influence on cellular function are unknown. It is proposed that inositol phosphates that serve as biologically important signaling molecules are responsible for the observed ` chemopreventive activity. Using well- established chemical methods, we intend to mimic these compounds with metabolically stable analogs. The action of the analogs on normal small airway epithelial (SAE) cells that have been treated with lung- specific carcinogens will be characterized. Relative activity and changes in cellular events linked to inositol signaling (i.e., Ca2+ mobilization) will be determined. We intend to define a structural framework for the influence of inositol compounds on carcinogen- exposed SAE cells and identify agents that display an enhanced aptitude for the suppression of lung cancer.
