Nicotine promotes the development of invasive bladder carcinoma in rats

Tobacco smoking is a major risk factor for human cancers including urinary bladder carcinoma. In a previous study, nicotine was shown to enhance rat urinary bladder carcinogenesis in a two-stage carcinogenesis model. In this study, we examined the progressive effects of nicotine on bladder carcinogenesis in F344 rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Nicotine, administered in drinking water for 52 weeks following 4 weeks of BBN treatment, significantly increased the incidence and multiplicity of invasive urothelial carcinoma in a dose-dependent manner. The Ki67 labeling index of bladder papillomas was significantly increased by nicotine in a dose-dependent manner. However, nicotine treatment did not affect the incidence or total number of tumors, and nicotine administration alone for 52 weeks did not result in any neoplastic lesions. These data suggest that while nicotine does not initiate carcinogenesis, it has the potential to promote invasive urinary cancers.