Chemopreventive effect of S-methylmethane thiosulfonate and sulindac administered together during the promotion/progression stages of colon carcinogenesis

S-methylmethane thiosulfonate (S-MMTS), isolated from cauliflower and havin g antiproliferative activity, and the non-steroidal anti-inflammatory drug sulindac have been shown to inhibit chemically induced colon carcinogenesis when they are administered during the initiation and/or post-initiation st ages. The present study was designed to investigate the chemopreventive eff icacy of 80 p.p.m. S-MMTS administered during the initiation and postinitia tion stages and of S-MMTS and sulindac administered together at low doses ( 40 and 160 p.p.m., respectively) during the promotion/progression phases (l ate in the premalignant stage) of colon carcinogenesis. At 5 weeks of age, groups of male F344 rats were fed diets containing 0 (control diet) or 80 p .p.m. S-MMTS. At 7 and 8 weeks of age all rats except those in the vehicle- treated groups were given s.c. injections of 15 mg/kg body wt azoxymethane (AOM). Rats receiving the control diet and intended for the study of inhibi tion of colon carcinogenesis during the promotion/progression phases were c ontinued on the control diet for 14 weeks after the second AOM treatment; t hey were then switched to experimental diets containing 80 p.p.m. S-MMTS, 1 60 p.p.m. sulindac or 40 p.p.m. S-MMTS plus 160 p.p.m. sulindac. The rats w ere maintained on their respective dietary regimens until 52 weeks after ca rcinogen treatment and were then killed. Colon tumors were evaluated histop athologically. Administration of 80 p.p.m. S-MMTS alone during the initiati on and post-initiation stages and promotion/progression stages had no signi ficant effect on colon tumor inhibition. In contrast, the administration of 160 p.p.m. sulindac during the promotion/progression stages did significan tly inhibit total colon tumor multiplicity (P < 0.05). Moreover, coadminist ration of 40 p.p.m. S-MMTS with 160 p.p.m. sulindac during the promotion/pr ogression stages suppressed the incidence and multiplicity of non-invasive adenocarcinomas (P < 0.05-0.01) and multiplicity of invasive and total aden ocarcinomas of the colon to a significant degree (P < 0.05-0.01). These fin dings have potential clinical implications.