Low colonic glutathione detoxification capacity in patients at risk for colon cancer

Colon carcinogenesis is a multifactorial process influenced by hereditary as well as environmental factors. The glutathione/glutathione S-transferase detoxification system in the colon is important for protection against carcinogens. We investigated the levels of glutathione/glutathione S-transferase in normal colon mucosa of patients with colorectal cancer and in patients at high risk for colorectal cancer compared with those in healthy controls. Glutathione content was analyzed by high-performance liquid chromatography, and glutathione S-transferase enzyme activity by spectrophotometric determination with 1-chloro 2,4-dinitrobenzene. Normal colon tissue of patients with colon adenoma (n = 64), colorectal cancer (n = 37), familial adenomatous polyposis (FAP; n = 19), hereditary non-polyposis colorectal cancer families with (HNPCC+Ad; n = 34) or without (HNPCC-Ad; n = 33) adenoma was investigated. Glutathione levels were significantly lower in the normal colon mucosa of patients with cancer, FAP, HNPCC-Ad or HNPCC+Ad compared with adenoma patients or healthy controls. Glutathione S-transferase enzyme activity in the distal colon was significantly lower in patients with cancer or FAP compared with the adenoma patients or healthy controls, whereas values in carcinoma patients were significantly lower compared with both the HNPCC-Ad and HNPCC+Ad groups. An association of low colonic glutathione/glutathione S-transferase activity levels and high clinical risk for the development of colorectal cancer was observed. This low glutathione detoxification capacity might contribute to the colon cancer risk.