Yamamoto M, Wu H H, Momose H, Rademaker A, Oyasu R
Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611-3008.
Cancer Res. 1992 Oct 1;52(19):5329-33.
Chronic urinary tract infection is an important risk factor for the development of carcinoma in the human urinary bladder. To test the effect of chronic persistent inflammation on bladder carcinogenesis, we instilled heat-killed Escherichia coli (1 x 10(8) cells suspended in 0.5 ml of phosphate-buffered 2.1% NaCl solution) twice a week into the heterotopically transplanted rat urinary bladders in which carcinogenesis was initiated by a single dose (0.25 mg) of N-methyl-N-nitrosourea. When compared with the control animals, the rats treated with killed E. coli showed significantly enhanced bladder tumorigenesis, as reflected by an increase in the incidence of tumor (P = 0.05) and a 6- to 40-fold increase in the number of tumors per bladder (P less than 0.0001). The tumors were characterized by intraepithelial clusterings of neutrophils and by chronic inflammation and marked capillary proliferation in the tumor stroma. All of these features were rare in tumors in the control groups. The accelerated cell proliferation induced by killed E. coli treatment appears to play a significant role in the enhancement of tumorigenesis.
慢性尿路感染是人类膀胱癌发生的一个重要危险因素。为了测试慢性持续性炎症对膀胱致癌作用的影响，我们每周两次将热灭活的大肠杆菌（1×10⁸个细胞悬浮于0.5 ml磷酸盐缓冲的2.1%氯化钠溶液中）注入异位移植的大鼠膀胱，这些膀胱的致癌作用由单剂量（0.25 mg）的N-甲基-N-亚硝基脲引发。与对照动物相比，用灭活大肠杆菌处理的大鼠膀胱肿瘤发生显著增强，表现为肿瘤发生率增加（P = 0.05）以及每个膀胱肿瘤数量增加6至40倍（P < 0.0001）。肿瘤的特征是中性粒细胞上皮内聚集、慢性炎症以及肿瘤基质中明显的毛细血管增生。所有这些特征在对照组肿瘤中很少见。灭活大肠杆菌处理诱导的细胞增殖加速似乎在肿瘤发生增强中起重要作用。
