INHIBITION OF 4-METHYLNITROSAMINO-3-PYRIDYL-1-BUTANONE

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The objective of this model is to develop a relatively rapid method for determining chemopreventive efficacy employing the NNK-induced lung tumor model in strain A mice. This specific model develops tumors histopathologically similar to those observed in human adenocarcinomas and exhibit many of the same genetic lesions including alterations in RB expression as well as mutations in the KiRas Oncogene. Typically this assay entails examining mice for a period of 16 weeks following treatment with NNK and then quantitating adenoma formation. In the proposed new methodology mice will be treated with NNK and followed for development of early histologic lesions after a period of 8-12 weeks. This should allow one to more rapidly quantitate the chemopreventive efficacy of the compounds under examination. A total of 10 chemopreventive agents, approximately half of which have previously been examined in a complete tumor assay, will be employed in the present assay. At least two of these agents glucocorticoid and phenethylisothiocyanate have previously been shown to be highly effective in the complete 16 week tumor assay.