Hoffmann A, Romen W, Neumann H G
Institute of Pharmacology and Toxicology, University of Würzburg, Federal Republic of Germany.
J Cancer Res Clin Oncol. 1993;119(6):329-34. doi: 10.1007/BF01208840.
trans-4-Acetylaminostilbene (AAS) is a complete carcinogen in rats and produces quite selectively tumors in Zymbal's glands. On the basis of DNA adduct formation, it has been proposed that this model arylamine initiates neoplastic transformation of cells in many tissues, particularly liver and kidney, which, in the classical sense are considered to be non-target tissues for this chemical. In the present study an initiating treatment with AAS was followed by unilateral nephrectomy and the application of two nephrotoxic substances, gentamycin or beta-cyclodextrin which, among other activities, stimulate cell proliferation specifically in kidney. The initiating dose of AAS, given alone, gave rise to Zymbal's gland and mammary tumors in female Wistar rats within 88 weeks but not to liver or kidney tumors. When the initiation treatment was followed by unilateral nephrectomy, alone or in combination with gentamycin, or by beta-cyclodextrin, four tumors in two out of ten animals, eight tumors in three/ten, and seven tumors in three/ten, respectively, were observed in the kidney. The administered dose of gentamycin was not sufficient to induce tumors on its own. The results support the view that the genotoxic effects of AAS produce promotable lesions in rat kidney. None of the animals that had been treated with AAS, with or without other treatments, developed tumors or the predominant types of preneoplastic lesions in the liver within 88 weeks; this supports the notion that liver, like kidney, is not a target for complete carcinogenesis for this chemical.
反式-4-乙酰氨基芪（AAS）在大鼠中是一种完全致癌物，并且相当选择性地在鼓室腺产生肿瘤。基于DNA加合物的形成，有人提出这种模型芳胺引发许多组织中细胞的肿瘤转化，特别是肝脏和肾脏，从传统意义上讲，这些组织被认为是该化学物质的非靶组织。在本研究中，先用AAS进行启动处理，然后进行单侧肾切除术，并应用两种肾毒性物质庆大霉素或β-环糊精，它们除其他作用外，还特别刺激肾脏中的细胞增殖。单独给予AAS的启动剂量在88周内使雌性Wistar大鼠发生鼓室腺和乳腺肿瘤，但未引发肝脏或肾脏肿瘤。当启动处理后进行单侧肾切除术，单独或与庆大霉素联合使用，或使用β-环糊精时，分别在十分之二的动物中观察到4个肾脏肿瘤，十分之三的动物中观察到8个肿瘤，十分之三的动物中观察到7个肿瘤。所给予的庆大霉素剂量本身不足以诱导肿瘤。结果支持以下观点，即AAS的遗传毒性作用在大鼠肾脏中产生可促进的病变。在88周内，无论是否接受其他治疗，接受AAS治疗的动物均未在肝脏中发生肿瘤或主要类型的癌前病变；这支持了肝脏与肾脏一样，不是该化学物质完全致癌作用的靶器官这一观点。
