Cotinine, a major nicotine metabolite, induces cell proliferation on urothelium in vitro and in vivo.

Cotinine, a major nicotine metabolite, induces cell proliferation on urothelium in vitro and in vivo. Toxicology. 2019 Oct 31;:152325 Authors: Suzuki S, Cohen SM, Arnold LL, Pennington KL, Kato H, Naiki T, Naiki-Ito A, Yamashita Y, Takahashi S Abstract Tobacco smoking is a major risk factor for human cancers including urinary bladder carcinoma. In a previous study, nicotine enhanced rat urinary bladder carcinogenesis using a rat urinary bladder two-stage carcinogenesis model. In the present study, nicotine metabolites (cotinine, trans-3'-hydroxy cotinine and N'-nitrosonornicotine) were evaluated in a cell proliferation assay using urinary bladder urothelial cell lines. Cotinine (0.1 to 1 mM) induced the highest cell proliferation compared to the others, including nicotine, in three bladder cancer cell lines (RT4, T24 and UMUC3 cells). By Western blot, cotinine induced phosphorylation of Stat3 and expression of cyclin D1 in UMUC3 cells. The cell proliferation induced by cotinine was blocked by inhibitors of nicotinic receptors (10 nM SR16584 or 10 µM methyllycaconitine citrate) and Stat3 (100 nM stattic). In an in vivo study, cotinine (13, 40 and 120 ppm) in drinking water also induced cell proliferation and simple hyperplasia in urinary bladder and renal pelvis urothelium of rats, but to a lesser degree compared to nicotine (40 ppm). Cytotoxicity detected by scanning electron microscopy and apoptosis in the bladder urothel...
Source: Toxicology - Category: Toxicology Authors: Tags: Toxicology Source Type: research