Journal of Toxicologic Pathology
Online ISSN : 1881-915X
Print ISSN : 0914-9198
ISSN-L : 0914-9198
Enhanced Urinary Bladder, Liver and Colon Carcinogenesis in Zucker Diabetic Fatty Rats in a Multiorgan Carcinogenesis Bioassay: Evidence for Mechanisms Involving Activation of PI3K Signaling and Impairment of P53 on Urinary Bladder Carcinogenesis
Naomi IshiiMin WeiAnna KakehashiKenichiro DoiShotaro YamanoMasaaki InabaHideki Wanibuchi
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2011 Volume 24 Issue 1 Pages 25-36


In the present study, modifying effects of diabetes on carcinogenesis induced in type 2 diabetes mellitus model Zucker diabetic fatty (ZDF) rats were investigated using a multiorgan carcinogenesis bioassay. Our results demonstrated enhancement of urinary bladder, colon and liver carcinogenesis in ZDF rats treated with five types of carcinogens (DMBDD). Elevated insulin and leptin and decreased adiponectin levels in the serum may be responsible for the high susceptibility of type 2 diabetes mellitus model rats to carcinogenesis in these organs. Possible mechanisms of increased susceptibility of diabetic rats to bladder carcinogenesis could be activation of the PI3K pathway and suppression of p53 in the urothelium in consequence of the above serum protein alterations.

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© 2011 The Japanese Society of Toxicologic Pathology
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