Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The direct effects of sodium saccharin and sodium cyclamate on the morphology of organ cultures of normal rat bladder have been studied by histology and scanning electron microscopy (SEM). Untreated cultures retained histologically normal urothelia up to 89 days with cell surface features characteristic of mature, fully differentiated superficial cells and maturing intermediate cells. Continuous treatment with either sodium saccharin (6 or 12 mM) or sodium cyclamate (12 or 24 mM) induced progressive abnormalities in the cultured urothelium. Acute toxicity was not seen but focal necrosis was observed with the higher dose of each compound and histological abnormalities were more severe with the higher doses. Sodium saccharin induced mild hyperplasia of the urothelium on the surface of the culture and foci of altered epithelial polarity from 14 days; abnormal nuclear staining plus changes in the basal lamina were evident from 28 days and were pronounced from 56 days onwards. Hyperplasia of the urothelium over the explants was mild but there were extensive epithelial outgrowths onto the culture support. In general, sodium cyclamate induced more severe changes than did sodium saccharin, with alterations in epithelial cell polarity plus basal cell changes from 14 days and focal nodular urothelial hyperplasia over the explant and gross hyperplasia between the explant and culture support and in the outgrowth from 28 days. The severe and rapid surface changes, evident by SEM, were similar both in saccharin-treated and in cyclamate-treated cultures. There was some early loss of superficial cells to reveal underlying immature cells which, together with the remaining mature cells, developed abnormal blebs and processes. From 14 days small immature cells were located at the culture surface between the mature cells. These were covered by a variety of membrane protrusions including long pleomorphic microvilli. Sodium cyclamate-treated cultures mostly had fewer small membrane protrusions than sodium saccharin-treated cultures but more pleomorphic microvilli. These morphological changes induced in the rat urothelium in vitro by direct treatment with sodium saccharin and sodium cyclamate are thus similar to those described previously in association with in vivo long-term feeding studies of sodium saccharin to rats and with both in vivo and in vitro treatment of the rat urothelium with the bladder carcinogen N-methyl-N-nitrosourea (MNU).
Carcinogenesis 1986 May
PMID:Induction of morphological changes in the urothelium of cultured adult rat bladder by sodium saccharin and sodium cyclamate. 242 38

Rat bladder epithelial cell transformation was found to involve at least three distinct phenotypic stages in vitro. The effects on this process of N-methyl-N-nitrosourea (MNU), sodium saccharin, sodium cyclamate and 12-O-tetradecanoylphorbol-13-acetate (TPA) alone or in combination were investigated. MNU was a potent inducer of proliferating preneoplastic epithelial foci. Sodium saccharin alone induced a transient hyperplastic response of the cultured urothelium but did not induce significantly more foci than in controls, though a late toxic effect of saccharin may have masked focus induction. In combination with a single dose of 250 micrograms/ml MNU, sodium saccharin did not increase focus incidence compared with MNU treatment alone but following a single treatment with 25 micrograms/ml MNU which alone induced no foci, saccharin induced a significant number of foci indicating a promoting effect under these conditions. Sodium cyclamate alone induced a marked and prolonged epithelial hyperplasia and a significant increase in focus incidence above controls and above MNU-treated cultures. Following a single treatment with 250 micrograms/ml MNU, cyclamate increased focus incidence still further. TPA, the potent skin tumour promoting agent, alone induced significantly more foci than in controls. Rapidly-proliferating cell lines were established from nine foci induced by treatment with MNU alone or MNU + saccharin. Four of these were tumorigenic. These results indicate that MNU is a potent inducer of preneoplastic foci in rat urothelial cultures. Sodium saccharin and sodium cyclamate can act as promoting agents in this in vitro system as in the in vivo induction of tumours and sodium cyclamate appears to be active as a complete inducer under these conditions.
Carcinogenesis 1986 Dec
PMID:Multistage transformation of cultured rat urothelium: the effects of N-methyl-N-nitrosourea, sodium saccharin, sodium cyclamate and 12-O-tetradecanoylphorbol-13-acetate. 243 Jul 29