Hoensch H, Peters W H M, Roelofs H M J, Kirch W
Department of Gastroenterology, General Hospital of Gross-Gerau, Gross-Gerau, Germany.
Curr Med Res Opin. 2006 Jun;22(6):1075-83. doi: 10.1185/030079906X112480.
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.
The expression of the components of the glutathione system in the colon was investigated with respect to age, gender and localisation.
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.
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 mug/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.
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.
谷胱甘肽S-转移酶（GST）可通过催化多种亲电试剂与还原型谷胱甘肽（GSH）结合，代谢内源性和外源性毒素及致癌物。GST酶活性的变化可能影响胃肠道某些部位发生癌症的易感性。
研究谷胱甘肽系统各成分在结肠中的表达与年龄、性别及部位的关系。
从208例因各种临床原因接受结肠镜检查的患者（106例女性，102例男性；平均年龄61岁）中，采集近端和远端结肠大体正常黏膜的活检组织。测定GSH含量、总GST酶活性以及GST同工酶谷胱甘肽S-转移酶P1（GSTP1）和谷胱甘肽S-转移酶M1（GSTM1）的水平。
从近端结肠到远端结肠，GST酶活性、GSH和GSTP1水平显著降低（GST活性：264对244 nmol/分钟/毫克蛋白，p<0.001；GSH含量：32对30 nmol/毫克蛋白，p = 0.022；GSTP1水平：2.25对2.10微克/毫克蛋白，p<0.001）。在女性患者中，从50岁以下到70岁以上，GST活性和GSTP1水平有显著的逐步升高。50至70岁女性患者中的口服性激素替代抑制了GST活性和GSTP1含量。
结肠黏膜中的GSH系统在远端结肠的表达水平低于横结肠；这种微小差异是否会转化为结直肠癌发病率的变化仍有待观察。随着年龄增长，女性表达的酶水平更高，而在男性中未发现显著的年龄效应。老年女性在结肠中可能比男性拥有更好的保护性GSH酶，这可能是女性结直肠癌发病率较低的原因之一。
