Petersen I, Ohgaki H, Ludeke B I, Kleihues P
Institut für Neuropathologie, Departement Pathologie, Zürich.
Verh Dtsch Ges Pathol. 1993;77:252-5.
We investigated 16 urothelial carcinomas from 13 patients with evidence of phenacetin abuse for p53 mutations by single-strand conformation polymorphism (SSCP) analysis and direct DNA sequencing. p53 mutations were detected in 8 of 14 primary tumors (57%). Missense mutations were located in exon 5 (3 mutations), exon 6 (1), exon 7 (2) and exon 8 (1). An insertion of a single cytosine in exon 5 was detected in a bladder tumor and its lung metastasis. In one patient, urothelial carcinomas in the renal pelvis and in the ureter exhibited two different mutations, strongly suggesting that these tumors developed independently. In contrast, the tumors in the renal pelvis and bladder of another patient contained the same mutation, indicating intracavitary metastatic spread. Our data support the view that phenacetin causes urothelial carcinomas through chronic tissue damage rather than promutagenic DNA lesions.
我们通过单链构象多态性（SSCP）分析和直接DNA测序，对13例有非那西丁滥用证据的患者的16例尿路上皮癌进行了p53突变研究。在14例原发性肿瘤中的8例（57%）检测到p53突变。错义突变位于外显子5（3个突变）、外显子6（1个）、外显子7（2个）和外显子8（1个）。在一例膀胱肿瘤及其肺转移灶中检测到外显子5中单一个胞嘧啶的插入。在一名患者中，肾盂和输尿管中的尿路上皮癌表现出两种不同的突变，强烈提示这些肿瘤是独立发生的。相反，另一名患者肾盂和膀胱中的肿瘤含有相同的突变，表明存在腔内转移扩散。我们的数据支持这样一种观点，即非那西丁通过慢性组织损伤而非促突变性DNA损伤导致尿路上皮癌。
