The primary objective of this workstatement is to investigate the chemopreventive efficacy of a variety of agents employing transgenic animals which have mutations similar to those found in humans and which spontaneously develop colon tumors. The first mouse model (Min mouse) has a mutation in the APC gene and develops multiple adenomas in a manner analogous to human FAP (familial adnomatous polyposis) patients. These mice will be employed to screen for four different potential chemopreventive agents. In addition two highly effective aspects will be employed to determine whether these agents are still effective one early, pre invasive, adenomas have arisen. The second animal model has a deficiency in the repair gene MSH-2 and appear comparable to humans with HNPCC (hereditary nonpolyposis colon cancer). These mice will be bred containing both APC and MSH-2 mutations will be bred and will be examined for chemopreventive efficacy employing a variety of chemopreventive agents. The results of these animal studies, employing these directly relevant models, are likely to be immediately applicable in determining agents for potential human trials.
