Prevention of urinary bladder tumors in cyclophosphamide-treated rats by additional medication with the uroprotectors sodium 2-mercaptoethane sulfonate (mesna) and disodium 2,2'-dithio-bis-ethane sulfonate (dimesna)

Cyclophosphamide (CP) was administered orally at a dose of 2.5 mg/kg body weight five times a week to 300 male Sprague-Dawley rats in a carcinogenicity experiment. Four groups of 50 rats were treated with two different doses of sodium 2-mercaptoethane sulfonate (mesna, Uromitexan) (single doses of 5 or 15 mg/kg body weight), or disodium 2,2'-dithio-bis-ethane sulfonate (dimesna) (single doses of 12 or 35 mg/kg body weight), and the effect on carcinogenicity by cyclophosphamide was investigated. Two groups received mesna or dimesna only, and one additional group of 100 rats served as an untreated control. Evaluation of the study after 20 months proved CP to be carcinogenic, the induced neoplasms being in a variety of organs including tumors of the urinary bladder in 30% of the rats. The additional administration of mesna and dimesna significantly reduced the bladder tumor risk, this reduction being dose-related. In the 100 rats treated with mesna or dimesna only, no evidence of a carcinogenic response or signs of other toxic effects were observed.