Distribution of 1,2 DMH-induced colonic aberrant crypt foci after administration of a gastrin receptor antagonist (CR2945), in the murine model.
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.
Fontana
M G
MG
Dept. of Surgery, University of Brescia.
Ghirardi
M
M
Moneghini
D
D
La Pinta
M
M
Villanacci
V
V
Donato
F
F
Salerni
B
B
D019813:1,2-Dimethylhydrazine; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D002273:Carcinogens; D003106:Colon / Q000187:drug effects / Q000473:pathology*; D003110:Colonic Neoplasms / Q000473:pathology; D008297:Male; D051379:Mice; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*
C116183:CR 2945; D002273:Carcinogens; D011949:Receptors, Cholecystokinin; D001569:Benzodiazepines; D019813:1,2-Dimethylhydrazine