Kawai K, Yamamoto M, Kameyama S, Kawamata H, Rademaker A, Oyasu R
Department of Pathology, Northwestern University Medical School, Chicago, Illinois.
Cancer Res. 1993 Nov 1;53(21):5172-5.
Chronic inflammation of the urinary tract is a significant risk factor for the development of urinary bladder cancer in humans. We previously demonstrated that weekly treatment with killed Escherichia coli enhanced rat urinary bladder tumorigenesis initiated by the carcinogen N-methyl-N-nitrosourea. We conducted the present study to determine whether lipopolysaccharide (LPS), a major cell wall component of E. coli, had a tumor-enhancing effect. LPS was instilled twice a week at three doses (100, 1.0, and 0.01 microgram/ml) into heterotopically transplanted rat urinary bladders which were treated with a single low dose (0.25 mg) of N-methyl-N-nitrosourea or vehicle. Rats treated with 100 micrograms/ml of LPS showed a significant increase in the incidence and number of tumors in the bladders pretreated with N-methyl-N-nitrosourea. Treatment with LPS alone did not induce tumors. The enhancing effects were associated with a marked increase in the numbers of polymorphonuclear leukocytes and an increase in the H2O2 concentration in the bladder lumen. Oxidative stress by reactive oxygen intermediates and a proliferative response of the carcinogen-exposed urothelium to the inflammatory stimulation appeared to play a significant role in tumor enhancement by LPS.
慢性尿路感染是人类膀胱癌发生的一个重要危险因素。我们之前证明，每周用灭活大肠杆菌进行治疗可增强由致癌物N-甲基-N-亚硝基脲引发的大鼠膀胱肿瘤发生。我们开展本研究以确定脂多糖（LPS）（大肠杆菌的一种主要细胞壁成分）是否具有肿瘤促进作用。将LPS以三种剂量（100、1.0和0.01微克/毫升）每周两次灌注入经单次低剂量（0.25毫克）N-甲基-N-亚硝基脲或赋形剂处理的异位移植大鼠膀胱中。用100微克/毫升LPS处理的大鼠，其经N-甲基-N-亚硝基脲预处理的膀胱中肿瘤的发生率和数量显著增加。单独用LPS处理未诱导肿瘤发生。这些促进作用与多形核白细胞数量的显著增加以及膀胱腔内过氧化氢浓度的增加有关。活性氧中间体引起的氧化应激以及暴露于致癌物的尿路上皮对炎症刺激的增殖反应似乎在LPS促进肿瘤方面发挥了重要作用。
