Chemopreventive effect of S-allylcysteine and its relationship to the detoxification enzyme glutathione S-transferase

Sulfur-containing substances derived from garlic and onion have been shown to prevent experimental carcinogenesis. One of the hypotheses explaining the mechanisms of the chemopreventive activity of these substances is that they activate detoxification systems such as glutathione S-trans-ferase (GST). In this study the effects of S-allylcysteine (SAC), a water-soluble organosulfur compound derived from garlic, on GST activities in the liver, small intestine and colon were investigated. Additionally, we examined SAC for chemopreventive effects on aberrant crypt foci, which are the most likely precursors of colon cancers. In the rat colonic aberrant crypt assay administration of SAC during the initiation period decreased the number of aberrant crypt foci by 33 and 54% in groups given 40 or 80% maximum tolerated dose (MTD) of SAC respectively. The number of aberrant crypt foci, however, was not changed when SAC was given during the promotion period. GST activity in the liver was increased significantly by 41% 12 h after a single oral administration of 3.5 mmol/kg SAC and this elevated GST level was maintained over a 72 h period. GST levels were increased significantly by the administration of SAC (1.8 mmol/kg/ day for 3 days) not only in the liver but also in the proximal and middle small bowel. Isozyme levels of GST after administration of SAC were also determined using Western blotting. Hepatic GST-α and GST-μ were significantly increased by 35 and 42% respectively after oral administration of SAC. GST-π levels were lower than the detection limit (130 ng/mg/protein) in both the control and SAC-treated groups. These results strongly support the previous working hypothesis that SAC exhibits chemopreventive activity by exerting specific effects on carcinogen detoxification systems.