Our previous experimental data demonstrated that a new
gastrin receptor antagonist (
CR2945) has a chemopreventive effect on
dimethylhydrazine-induced
colon cancer in mice. The aim of this study is to test the effect of
CR2945 on the appearance and distribution of
aberrant crypt foci (ACF), proposed as early "preneoplastic" lesions in colon
carcinogenesis, in the murine model. 176 CD1 male mice were randomly divided into 4 groups: group 1,
sham group received 2 daily intra-peritoneal
injections of
saline solution; group 2 received 1 weekly intra-peritoneal injection of
DMH 20 mg/kg, for 5 weeks, and 2 daily intra-peritoneal
injections of equal volume of NaCl 0.9%; group 3 and 4 received the same weekly dose of
DMH and 2 daily
injections of
CR2945 at the respective doses of 2.5 and 7.5 mg/Kg for 5 weeks. The rodents were sacrified 15, 20, 25, and 38 weeks after receiving the first injection. The number of ACF per area (ACF frequency), their multiplicity (number of crypts per focus), ACF frequency according to each colonic site were recorded. No ACF were found in the
sham group. No substantial differences were observed in ACF distribution between the remaining groups. Our hypothesis is that
CR2945 does not alter the final number of ACF but might induce a regression of some dysplastic ACF.