Expression of the glutathione enzyme system of human colon mucosa by localisation, gender and age

Background: The glutathione S-transferases ( GST) can metabolise endogenous and exogenous toxins and carcinogens by catalysing the conjugation of diverse electrophiles with reduced glutathione ( GSH). Variations of GST enzyme activity could influence the susceptibility of developing cancers in certain areas of the gastrointestinal tract. Aims: The expression of the components of the glutathione system in the colon was investigated with respect to age, gender and localisation. Methods: Biopsies of macroscopically normal mucosa from both proximal and distal colon were collected from 208 patients ( 106 females, 102 males; mean age 61 years), who underwent colonoscopy for various clinical reasons. GSH content, total GST enzyme activity and the levels of the GST isoenzymes glutathione S-transferase P1 ( GSTP1) and glutathione S-transferase M1 ( GSTM1) were determined. Results: GST enzyme activity, GSH and GSTP1 levels decreased significantly from proximal to distal colon ( GST activity: 264 vs. 244 nmol/min/mg protein, p < 0.001, GSH content: 32 vs. 30 nmol/mg protein, p = 0.022 and GSTP1 levels: 2.25 vs. 2.10 mu g/mg protein, p < 0.001). In female patients there was a significant stepwise increase of GST-activities and GSTP1 levels from the age of under 50 years to over 70 years. Oral sex hormone substitution among female patients between 50 and 70 years suppressed GST-activities and GSTP1 content. Conclusions: The GSH-system in the colonic mucosa is expressed at a lower level in the distal colon ( sigma) than in the colon transversum; whether this small difference translates into variations of incidence of colorectal cancer remains to be seen. Females express higher enzyme levels as they grow older, while in males no significant age effects were found. Elderly females might be better equipped with protective GSH-enzymes in the colon than males and this could contribute to the lower incidence of colorectal carcinomas in females.