Abstract:
Objective To study the cell cycle regulatory mechanism in rat bladder carcinogenesis promoted by terephthalic acid (TPA).
Methods A total of 50 male Wister rats were divided into test group (30 rats) and control group (20 rats), respectively intraperitoneally injected with N-methyl-N-nitrosourea (MNU) and citrate buffer twice a week for 4 weeks, and then basal diet containing 5%TPA were given to the test group and basal diet to the control group separately for the next 22 weeks. Major regulatory proteins in G1 cell cycle checkpoint including p16INK4a, cyclin-dependent kinase 4 (Cdk4), cyclin D1, and retinoblastoma protein (pRb) were determined during various stages of urinary bladder carcinogenesis by immunohistochemistry.
Results In MNU-5% TPA treated group, the incidences of overexpression of Cdk4, cyclin D1 and pRb in papilloma were significantly higher than those in epithelial simple hyperplasia (P=0.023, P < 0.001 and P < 0.001, respectively) and in papillary or nodular (PN) hyperplasia (P=0.042, P=0.012 and P=0.002, respectively). The incidence of absent expression of p16INK4a in papilloma was much higher than that in epithelial simple hyperplasia (P=0.004) and in PN hyperplasia (P=0.02).
Conclusion Our results clearly reveal that the disorder of p16INK4a-cyclin D1/Cdk4-pRb pathway is associated with bladder carcinogenesis promoted by TPA-stone.
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