Abstract | OBJECTIVE: METHODS: A total of 112 weanling male SD rats that divided between six groups were given basal diet (control), diets containing 5% TPA or in combination with either 4% sodium NaHCO3 or 0.02% hydrochlorothiazide. After 90-day feeding, bladder samples were collected for histopathological diagnoses, and immunohistochemical method was used to characterize the expression of p16Ink4a cyclin D1, CDK4, EGFr and cyclin E in relation to that of proliferating cell nuclear antigen ( PCNA). RESULTS: In TPA treatment groups, bladder stone incidence was 40% (21/52) with 14 cases of proliferative bladder. In control and other groups, neither stone nor epithelial cell proliferation was diagnosed. PCNA-positive focal hyperplasic lesions involved all epithelial layers. Overexpressions of cyclin D1, CDK4, EGFr are found in the corresponding lesion. p16Ink4a nuclear staining reduced in proliferative bladders especially with a great quantity of stone. In addition, no positive expression was detected on cyclin E. CONCLUSION: The present study provides a strong evidence of a link between induction of bladder hyperplasia, deregulation of the p16Ink4a-cyclin D1/CDK4 pathway, and abnormal EGFr mediated signal transduction pathway.
|
Authors | Guidong Dai, Lunbiao Cui, Ling Song, Jianfeng Cheng, Yihong Zhong, Renzhen Zhao, Xinru Wang |
Journal | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
(Food Chem Toxicol)
Vol. 43
Issue 2
Pg. 217-24
(Feb 2005)
ISSN: 0278-6915 [Print] England |
PMID | 15621333
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Cyclin E
- Cyclin-Dependent Kinase Inhibitor p16
- Free Radical Scavengers
- Phthalic Acids
- Proliferating Cell Nuclear Antigen
- Proto-Oncogene Proteins
- Hydrochlorothiazide
- Cyclin D1
- terephthalic acid
- Sodium Bicarbonate
- ErbB Receptors
- Cdk4 protein, rat
- Cyclin-Dependent Kinase 4
- Cyclin-Dependent Kinases
|
Topics |
- Animals
- Cell Division
(drug effects, physiology)
- Cocarcinogenesis
- Cyclin D1
(metabolism)
- Cyclin E
(metabolism)
- Cyclin-Dependent Kinase 4
- Cyclin-Dependent Kinase Inhibitor p16
- Cyclin-Dependent Kinases
(metabolism)
- Epithelial Cells
(cytology, drug effects)
- ErbB Receptors
(metabolism)
- Free Radical Scavengers
(adverse effects)
- G1 Phase
(drug effects, physiology)
- Hydrochlorothiazide
(pharmacology)
- Hyperplasia
(chemically induced)
- Immunohistochemistry
- Male
- Phthalic Acids
(adverse effects)
- Proliferating Cell Nuclear Antigen
(metabolism)
- Proto-Oncogene Proteins
(metabolism)
- Random Allocation
- Rats
- Rats, Sprague-Dawley
- S Phase
(drug effects, physiology)
- Sodium Bicarbonate
(pharmacology)
- Urinary Bladder
(drug effects, pathology)
- Urinary Bladder Calculi
(chemically induced, epidemiology, pathology)
|