In vitro neoplastic transformation of epithelial cells of rat urinary bladder by nitrosamines

Nature ◽  
1974 ◽  
Vol 252 (5483) ◽  
pp. 497-499 ◽  
Author(s):  
YOSHIYUKI HASHIMOTO ◽  
HISAYO S. KITAGAWA
Keyword(s):  
Epithelial Cells ◽  
Urinary Bladder ◽  
Neoplastic Transformation ◽  
Rat Urinary Bladder

Release of cyclic AMP by toad urinary bladder

1975 ◽  
Vol 228 (3) ◽  
pp. 954-958 ◽  
Author(s):  
S Urakabe ◽  
JS Handler ◽  
J Orloff
Keyword(s):  
Epithelial Cells ◽  
Urinary Bladder ◽  
Cyclic Amp ◽  
Cell Membrane ◽  
Water Permeability ◽  
Ringer Solution ◽  
Mucosal Surface ◽  
Toad Urinary Bladder ◽  
Solution Bathing

Cyclic AMP accumulates in the Ringer solution bathing the toad urinary bladder in vitro. At least 4 times more cyclic AMP is released into the solution bathing the serosal surface than into the solution bathing the mucosal surface. Most of the cyclic AMP originates in the epithelial cells rather than the stroma. Vasopressin increased the content of cyclic AMP in the epithelial cells and increases the amount of cyclic AMP in the Ringer solution. Since there is not an increase in medium cyclic AMP when cell cyclic AMP levels are increased by theophylline, it is suggested that theophylline may reduce the permeability of the cell membrane to cyclic AMP. Finally, it is demonstrated that 10 mM NaF increase the amount of cyclic AMP in the epithelial cells and in the solution bathing the bladder, but block the effect of vasopressin on water permeability, presumably at a step subsequent to the formation of cyclic AMP.

scholarly journals Neoplastic transformation of epithelial cells in whole mammary gland in vitro.

1979 ◽  
Vol 76 (11) ◽  
pp. 5886-5890 ◽  
Author(s):  
N. T. Telang ◽  
M. R. Banerjee ◽  
A. P. Iyer ◽  
A. B. Kundu
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Neoplastic Transformation

scholarly journals Rat Urinary Bladder Carcinogenesis by Dual-Acting PPARα+γAgonists

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-14 ◽  
Author(s):  
Martin B. Oleksiewicz ◽  
Jennifer Southgate ◽  
Lars Iversen ◽  
Frederikke L. Egerod
Keyword(s):  
Urinary Bladder ◽  
Mode Of Action ◽  
Carcinogenic Effect ◽  
Attrition Rates ◽  
Rat Urinary Bladder ◽  
Mediated Effects ◽  
Kidney Pelvis ◽  
Rats And Mice

Despite clinical promise, dual-acting activators of PPARαandγ(here termed PPARα+γagonists) have experienced high attrition rates in preclinical and early clinical development, due to toxicity. In some cases, discontinuation was due to carcinogenic effect in the rat urothelium, the epithelial layer lining the urinary bladder, ureters, and kidney pelvis. Chronic pharmacological activation of PPARαis invariably associated with cancer in rats and mice. Chronic pharmacological activation of PPARγcan in some cases also cause cancer in rats and mice. Urothelial cells coexpress PPARαas well as PPARγ, making it plausible that the urothelial carcinogenicity of PPARα+γagonists may be caused by receptor-mediated effects (exaggerated pharmacology). Based on previously published mode of action data for the PPARα+γagonist ragaglitazar, and the available literature about the role of PPARαandγin rodent carcinogenesis, we propose a mode of action hypothesis for the carcinogenic effect of PPARα+γagonists in the rat urothelium, which combines receptor-mediated and off-target cytotoxic effects. The proposed mode of action hypothesis is being explored in our laboratories, towards understanding the human relevance of the rat cancer findings, and developing rapid in vitro or short-term in vivo screening approaches to faciliate development of new dual-acting PPAR agonist compounds.

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