Maytansine as a cause of acute proliferative disorder of bladder urethelium in the rat

Male Wistar Lewis rats were injected with maytansine at a total dose of 0.425 to 0.6 mg/kg over a 3-week period. Biopsies taken at 5 weeks showed that 23% of the bladders had hyperplasia or other abnormalities. Of the bladder biopsies done for the first time at 8 weeks, 80% demonstrated papillary hyperplasia. A small number of biopsies at 13 and 19 weeks still showed hyperplasia and minimal inflammatory reaction. These results were seen regardless of prior biopsy, the presence of bladder calculi, and/or the dose level used. It is not clear from the data whether the observed changes are reversible or precarcinogenic. However, these changes closely resembled the histologic features described in the evolution of bladder cancer in rats fed N-C4-(5-nitro-2-furyl)-2-thiazolyl formamide.