Further investigations on the proliferative response of mouse bladder epithelium to 4-ethyl-sulphonylnaphthalene-1-sulphonamide.
1969; Springer Nature; Volume: 23; Issue: 4 Linguagem: Inglês
10.1038/bjc.1969.96
ISSN1532-1827
AutoresФ. К. Джиоев, M Wood, D M Cowen, O Campobasso, David B. Clayson,
Tópico(s)Polyamine Metabolism and Applications
Resumo4-ETHYLSULPHONYLNAPHTHALENE-1-SULPHONAMIDE (ENS*) induces hyper- plasia of the bladder epithelium on administration to rats (Paget, 1958) and mice (Sen Gupta, 1962).Bladder tumours result from prolonged feeding of ENS to mice (Clayson and Bonser, 1965; Clayson, Pringle and Bonser, 1967).Hyper- plasia is more severe and tumcours are more frequent in female than in male mice.The acute response to a single oral dose of ENS has been studied in some detail (Clayson et al., 1967; Lawson, Dzhioev, Lewis and Clayson, 1968; Levi, Cowen and Cooper, 1969).An increase in DNA synthesis, in the normally quiescent bladder epithelium, is induced at about 16 hours after the administration of the chemical, rises to a maximum at 30-36 hours and thereafter slowly declines.RNA synthesis, necessary for the increase in enzymes for DNA synthesis, occurs during the lag phase.Detailed histopathological, autoradiographic and stathmokinetic investi- gations show that DNA synthesis and subsequent mitosis occur in every cell layer and involve cells of all ploidies in this epithelium, in contradistinction to the behaviour of other multilayered epithelia in which DNA synthesis and mitosis is restricted to the basal layers.The present paper describes experiments to determine (i) the effect of treat- ment with ENS for varying periods on the induction of bladder tumours and (ii) the state of the epithelium at various times during tumour induction. MATERIALS AND METHODSAnimals.-A x IF F1 hybrid mice were bred in the laboratory and maintained on Oxoid 41B diet and water ad libituMn.All mice were vaccinated against ectro- melia before entering the experiment and were started on ENS at 10-14 weeks of age.Chemicals.-ENS was prepared in the laboratory by the method of Brimelow and Vasey (1958) and made up into the diet as described by Clayson et al. (1967).For administration by stomach tube, ENS (0.5%) was suspended in microcrystal- line form in aqueous propylene glycol and stabilised by mucilage of tragacanth (Levi et al., 1969).6-[3H]-thymidine ([3H-TdR; 5000 mCi/m-mole) was obtained from the Radiochemical Centre, Amersham.Preparation of Tissues.-Mice were killed with ether, the bladder distended with Bouin's fixative and with selected pieces of other tissues was fixed in the same
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