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.