Chalcones, myo-inositol and other novel inhibitors of pulmonary carcinogenesis.

The objective of the studies reported here has been to find novel chemopreventive agents effective against carcinogenesis of the lung. In particular, identification of suppressing agents, i.e., compounds preventing the evolution of the neoplastic process, has been sought. For this purpose, inhibition of pulmonary neoplasia in female A/J mice given the test agent starting one week after the last administration of three doses of benzo[a]pyrene has been employed as the experimental model. Under these conditions, chalcone, 4'-methoxychalcone,myo-inositol, dexamethasone, and "terpeneless" orange oil added to the diet suppressed pulmonary adenoma formation. Chalcone and 4'-methoxychalcone are open chain flavonoids, neither of these compounds occurs naturally, and their mechanism of action is not known. myo-Inositol is a naturally occurring compound of particular interest because of its exceedingly low toxicity. Dexamethasone is a potent glucocorticoid. Amongst its biological properties is the capacity to induce maturation of Type 2 alveolar cells and to stimulate production of surfactant by these cells. "Terpeneless" orange oil is a fraction of orange oil consisting predominantly of compounds with carbonyl or hydroxyl groups. The constituent or constituents responsible for the inhibitory effects observed is not known. The above studies are in an early phase of development and their ramifications remain to be determined.