Mekhail-Ishak K, Hudson N, Tsao M S, Batist G
Department of Medicine, Montreal General Hospital, Quebec, Canada.
Cancer Res. 1989 Sep 1;49(17):4866-9.
Human colonic tissue is exposed to a variety of toxic chemicals and potential carcinogens in the diet and the intestinal microenvironment. Colonic adenocarcinoma is commonly resistant to the cytotoxic effects of most chemotherapeutic drugs. We have examined drug metabolic and detoxification pathways in clinical specimens of colon carcinoma and normal adjacent mucosa from 17 patients. All elements of xenobiotic metabolism examined are present in these tissues, including cytochrome P-450-dependent enzymes, glutathione, and glutathione-utilizing enzymes. In comparison of tumor tissue to its respective normal mucosa specific alterations in the pathways affecting a number of chemotherapeutic agents were detected, including significantly higher glutathione, glutathione peroxidase, and anionic glutathione-S-transferase activity. These and other alterations found here could be the target of therapeutic maneuvers to enhance the efficacy of antineoplastic treatment of human colon cancer.
人类结肠组织在饮食和肠道微环境中会接触到多种有毒化学物质和潜在致癌物。结肠腺癌通常对大多数化疗药物的细胞毒性作用具有抗性。我们检测了17例患者结肠癌临床标本及相邻正常黏膜中的药物代谢和解毒途径。所检测的外源性物质代谢的所有成分在这些组织中均有存在，包括细胞色素P - 450依赖性酶、谷胱甘肽以及利用谷胱甘肽的酶。将肿瘤组织与其各自的正常黏膜进行比较时，发现影响多种化疗药物的途径存在特定改变，包括谷胱甘肽、谷胱甘肽过氧化物酶和阴离子型谷胱甘肽 - S - 转移酶活性显著更高。此处发现的这些及其他改变可能成为提高人类结肠癌抗肿瘤治疗疗效的治疗策略的靶点。
