Chemoprevention of lung cancer by isothiocyanates and their conjugates in A/J mouse.

The discovery of dietary-related compounds with potential to inhibit lung cancer may present promising and practical approaches for reducing the risk of lung cancer caused by smoking. To this end, we have conducted mechanism-based bioassays in A/J mice over the years to screen compounds, particularly isothiocyanates (ITCs) in the crucifer family, and studied their modes of action against lung tumorigenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a nicotine-derived lung carcinogen. These studies have shown that A/J mice serve as a practical and useful model for the study of lung cancer prevention. The studies described here illustrate the value of using the A/J mouse model in the bioassays and the structural-activity relationship, metabolism, and mechanism investigations. One of the important features of the A/J mouse model is that a single dose of NNK induces a significant number of lung tumors within 16 weeks. This feature offers a prerequisite for in vivo screening as well as for dissecting the initiation or the postinitiation effect of ITCs and their conjugates during lung tumor development. Our recent bioassays in A/J mice demonstrate that ITC conjugates are versatile chemopreventive agents capable of inhibiting NNK-induced lung tumorigenesis during both the initiation and the postinitiation phases. These findings are of importance, considering the potential of these agents as chemopreventive agents for lung cancer in smokers and ex-smokers.