Morphological effects of mitomycin C on urothelial responses to experimentally-induced urethral stricture in rats

• Published in: International journal of urology Vol. 22; no. 7; pp. 702 - 709
• Main Authors: Chang, In Youb, Kim, Jin Nam, Kim, Sun-Ouck, Han, Misook, Huh, Jung-Sik, Maeng, Young Hee, Yoon, Sang Pil
• Format: Journal Article
• Language: English
• Published: Australia Blackwell Publishing Ltd 01.07.2015
• Subjects: Animals; apurinic/apyrimidinic endonuclease 1; Cell Proliferation; Disease Models, Animal; DNA Damage; Male; Mitomycin - administration & dosage; mitomycin C; Nucleic Acid Synthesis Inhibitors - administration & dosage; proliferating cell nuclear antigen; Rats; Rats, Sprague-Dawley; Urethra - pathology; Urethra - surgery; urethral stricture; Urethral Stricture - drug therapy; urothelium; Urothelium - drug effects; Urothelium - physiopathology; proliferating cell nuclear antigen; apurinic/apyrimidinic endonuclease 1; urethral stricture; mitomycin C; urothelium
• ISSN: 0919-8172; 1442-2042
• DOI: 10.1111/iju.12780

Objectives To analyze the urothelial responses to mitomycin C treatment after urethral injury in rats, as the urothelium might play a role in the pathogenesis of urethral stricture. Methods Male Sprague–Dawley rats were divided into four groups (n = 5/group): negative control, positive control without further treatment, experimental control treated with sodium hyaluronate and sodium carboxymethylcellulose, and experimental treated with mitomycin C after internal urethrotomy. Results Compared with negative controls, positive controls showed a significant increase in cell proliferation and DNA damage accompanied by a considerable decrease in DNA repair in the urothelium, which resulted in urethral stricture. Experimental controls showed a significant increase in cell proliferation, DNA damage and DNA repair compared with negative controls. The mitomycin C‐treated group showed a significant decrease in cell proliferation and DNA damage, but a considerable increase in DNA repair compared with the positive and experimental control groups. DNA damage was immediately increased after urethral injury, but DNA repair and cell proliferation showed belated and upregulated expression after mitomycin C treatment. Conclusions Mitomycin C could induce healthy re‐epithelialization without severe damage in the urothelium. This finding might support the possibility of using mitomycin C as an adjuvant therapy for urethral strictures, and it might also suggest a urothelial role in the process of urethral stricture after urethral injury.