Journal
TOXICOLOGY LETTERS
Volume 170, Issue 2, Pages 116-123Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2007.02.011
Keywords
p-Phenylenediamine; urothelial carcinoma; cyclooxygenase; p53
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p-Phenylenediamine (p-PD) is the main aromatic amine used in the formulation of hair dyes. Some epidentiologic studies have suggested that the use of p-PD-based hair dyes might be related to increased risk of human malignant tumors including bladder cancer and hematopoietic cancers. However, the toxicity and genotoxicity of p-PD on urothelial cells has not been reported yet. Therefore, we investigated the genotoxicity of p-PD on human urothelial cells and study its association with the expression of oncoproteins p53 and cyclooxygenase-2 (COX-2). Our results revealed that p-PD was able to induce DNA damage determined by Comet assay. In addition, our immunocytochemical and Western blotting results showed that p-PD induced overexpression of mutant p53 and COX-2 in a dose-dependent manner. The relationship between mutant p53 and COX-2 expression shows strong correlation. Furthermore, the accumulation of mutant p53 was linearly correlated with Comet scores. These results suggest that p-PD can induce DNA damage and accumulation of mutant p53 and COX-2 proteins; this may be one of the possible mechanisms that cause genotoxic carcinogenesis in the urothelial cells. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
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