Tsuda H, Inoue T, Asamoto M, Fukushima S, Ito N, Okamura T, Ohtaguro K, Washida H, Satoh K, Amelizad Z
First Department of Pathology, Nagoya City University Medical School, Japan.
Virchows Arch B Cell Pathol Incl Mol Pathol. 1989;56(5):307-16. doi: 10.1007/BF02890031.
The expression of a number of enzymes involved in drug metabolism, membrane function etc. was compared in hyperplastic and neoplastic lesions of the rat bladder and in human bladder tumours. Transitional cell carcinomas (TCC) in both rat and Man were characterized by decreased alkaline phosphatase (ALP) and increased gamma-glutamyl transpeptidase (GGT), beta-glucuronidase (beta-G1), succinate dehydrogenase (SD) and glucose-6-phosphate dehydrogenase (G6PD) activities. In addition, binding for antibodies specific for different cytochrome P-450 species (UT50, PB3a, MC1, MC2) and microsomal epoxide hydrolase (mEHb) was elevated in both murine and human tumours. Comparison of the enzyme phenotype in hyperplastic lesions induced by freeze ulceration or uracil administration with that in preneoplastic papillary or nodular hyperplasia (PNH) and TCC suggested, however, that most of the alteration in enzyme content or activity was non-specific and related to requirements for epithelial cell proliferation. On the other hand, the decreased ALP, and increased GGT and beta-G1 activity appeared more directly related to neoplastic transformation. The results suggested that qualitative differences exist between reactive hyperplasia and preneoplastic or neoplastic lesions in the urinary bladder. The finding of increased cytochrome P-450, in clear contrast to the reduction characteristic of preneoplastic hepatic lesions, may be important with regard to the observed difference in neoplastic transformation between the bladder and liver in response to drug metabolising enzyme inducers.
对参与药物代谢、膜功能等的多种酶在大鼠膀胱的增生性和肿瘤性病变以及人类膀胱肿瘤中的表达进行了比较。大鼠和人类的移行细胞癌(TCC)的特征均为碱性磷酸酶(ALP)活性降低,γ-谷氨酰转肽酶(GGT)、β-葡萄糖醛酸酶(β-G1)、琥珀酸脱氢酶(SD)和葡萄糖-6-磷酸脱氢酶(G6PD)活性升高。此外,在鼠类和人类肿瘤中,针对不同细胞色素P-450亚型(UT50、PB3a、MC1、MC2)和微粒体环氧化物水解酶(mEHb)的抗体结合均增加。然而,将冷冻溃疡或尿嘧啶给药诱导的增生性病变中的酶表型与癌前乳头状或结节性增生(PNH)及TCC中的酶表型进行比较表明,酶含量或活性的大多数改变是非特异性的,且与上皮细胞增殖的需求有关。另一方面,ALP降低以及GGT和β-G1活性增加似乎与肿瘤转化更直接相关。结果表明,膀胱反应性增生与癌前或肿瘤性病变之间存在质的差异。细胞色素P-450增加这一发现,与癌前肝脏病变的特征性降低形成鲜明对比,这对于观察到的膀胱和肝脏在对药物代谢酶诱导剂的肿瘤转化方面的差异可能具有重要意义。