p-Phenylenediamine induced DNA damage in SV-40 immortalized human uroepithelial cells and expression of mutant p53 and COX-2 proteins.
p-Phenylenediamine (p-PD) is the main aromatic amine used in the formulation of hair dyes. Some epidemiologic 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.
Huang
Ya-Chun
YC
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Hung
Wen-Chun
WC
Kang
Wan-Yi
WY
Chen
Wan-Tzu
WT
Chai
Chee-Yin
CY
D015153:Blotting, Western; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D002472:Cell Transformation, Viral; D004396:Coloring Agents / Q000633:toxicity*; D020552:Comet Assay; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D010655:Phenylenediamines / Q000633:toxicity*; D013539:Simian virus 40 / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D019459:Urothelium / Q000187:drug effects* / Q000378:metabolism / Q000821:virology
D004396:Coloring Agents; D009153:Mutagens; D010655:Phenylenediamines; D016159:Tumor Suppressor Protein p53; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; C029728:4-phenylenediamine