betadex and Cocarcinogenesis

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.

Topics: Adenoma, Chromophobe; Animals; beta-Cyclodextrins; Carcinogens; Cocarcinogenesis; Cyclodextrins; Cystadenoma; Female; Gentamicins; Kidney Neoplasms; Nephrectomy; Rats; Rats, Wistar; Stilbenes

1,2-Dichlorovinylcysteine (DCVC) is known to cause enlarged nuclei in renal proximal tubule epithelium. This study further characterized the cellular changes induced by DCVC. Also a preliminary investigation of the initiator and promoter potential of DCVC was conducted. When given for 4 weeks in drinking water to Swiss-Webster mice, DCVC (50 or 100 micrograms/ml) caused a progressive change in renal epithelia which was persistent at 23 weeks. Enlarged nuclei with uneven chromatin dispersal, multiple nucleoli, and irregular nuclear membranes resided in enlarged, abnormally-shaped cells. These changes were resolved by week 50. Mice initiated with dimethylnitrosamine developed renal tumors by week 27. Mice fed DCVC (10 or 50 micrograms/ml) for 14 weeks following dimethylnitrosamine initiation, had a slightly higher tumor incidence, a higher incidence of invasive tumors, and had multiple renal tumors unlike animals given dimethylnitrosamine alone.

Topics: Animals; beta-Cyclodextrins; Cocarcinogenesis; Cyclodextrins; Cysteine; Dimethylnitrosamine; Drug Synergism; Kidney; Kidney Neoplasms; Mice

Injection (sc) of beta-cyclodextrin (beta-C) increased the number and size of renal tubular cell tumors in inbred Wistar (W) rats treated with 1,000 ppm of N-ethyl-N-hydroxyethylnitrosamine (EHEN). The incidence of renal tumors at the end of the 32-week experiment was 50% in rats treated with 1,000 ppm EHEN for 2 weeks and 100% in rats treated with 1,000 ppm EHEN for 2 weeks and then given daily sc injections of beta-C for 1 week. The incidence of renal tumors more than 3 mm in diameter was 70% in rats treated with 1,000 ppm EHEN before beta-C but 0% in rats treated with EHEN alone. In addition, beta-C promoted the development of renal tumors in rats treated with 500 ppm EHEN, which is a subthreshold dose for renal tubular cell tumorigenesis. These results show that beta-C promotes EHEN-induced renal tubular cell tumorigenesis.

Topics: Animals; beta-Cyclodextrins; Body Weight; Carcinogens; Cocarcinogenesis; Cyclodextrins; Dextrins; Diet; Diethylnitrosamine; Kidney Cortex; Kidney Neoplasms; Kidney Tubules; Male; Nitrosamines; Organ Size; Rats; Rats, Inbred Strains; Starch