Chemopreventive effect of 2-(allylthio)pyrazine (2-AP) on rat colon carcinogenesis induced by azoxymethane (AOM)

An investigation was conducted to assess the chemopreventive effects of 2-( allylthio)pyrazine (2-AP), synthesized for potential use as a chemopreventi ve agent, after administration during the pre-initiation and post-initiatio n stages in a rat colon carcinogenesis model with azoxymethane (AOM). One h undred, 5-week-old, male F344 rats were randomly divided into two experimen ts (n = 50 each). Experiment 1 rats were randomly divided into three groups : Group 1 rats: were pre-treated with 2-AP (25 or 50 mg/kg body weight, 3 c onsecutive days through the route of intragastric intubations) before AOM ( 20 mg/kg body weight, single subcutaneous (s.c.) injection) initiation. Gro up 2 rats were treated with AOM alone. Group 3 rats were given 2-AP alone w ithout AOM initiation. The animals were killed at the end of each experimen t (week 5) and the aberrant crypt foci (ACF) of the colonic mucosa were ass essed after staining with methylene blue. Experiment 2 rats were randomly d ivided into three groups: Group 1 rats: were given 2-AP (10, 25 or 50 mg/kg body weight, five-times intragastric intubations per week for 5 weeks from week 3) after AOM (15 mg/kg body weight, three s.c, injections) initiation for 2 weeks. Group 2 rats were treated with AOM alone. Group 3 rats were g iven 2-AP alone without AOM initiation. The animals were killed at the end of the experiment (week 8) and the ACF of the colonic mucosa were quantifie d. Total numbers of ACF/colon in Group 1 rats: (pre-treated with 2-AP) tend ed to decrease (2-AP, 50 mg/kg body weight) or increase (2-AP, 100 mg/kg bo dy weight) depending on the dose level. Total numbers of ACF/colon in Group 1 rats (treated with AOM followed by 2-AP, all subgroups; 160.8 +/- 38.0; 161.8 +/- 38.1; 137.1 +/- 48.4) were decreased significantly compared with the values in Group 2 rats (AOM alone; 214.8 +/- 48.1) (P < 0.05 or 0.01). The highest dose group (2-AP, 50 mg/kg body weight) had the lowest levels o f total numbers of ACF/colon among the three subgroups. Total numbers of ab errant crypts (AC)/colon of the highest dose I:roup (340.1 +/- 117.9) decre ased significantly compared with the value for Group 2 rats (AOM alone; 545 .1 +/- 38.3). These results thus suggest that 2-AP may have potential as a chemopreventive agent against rat colon carcinogenesis after administration of AOM during the post-initiation stage. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.