Bladder epithelial hyperplasia in F344 rats after intravesical instillation of the antitumor chemotherapeutic agents Adriamycin and mitomycin C.

The effects of intravesical instillation of the antineoplastic antibiotics, Adriamycin or mitomycin C, on the urinary bladder epithelium of female F344 rats were evaluated using a combined immunohistochemical and morphological approach. Four weeks treatment with Adriamycin or mitomycin C induced an increase of DNA synthesis and was associated with simple hyperplasia characterized by elevated nuclear cytoplasmic ratios, cytomegaly and pleomorphism. Under the scanning electron microscope (SEM), luminal cell surface alterations such as pleomorphic microvilli were observed. Severity of the lesions was greatest in the Adriamycin group and although treatment of the saline vehicle alone also brought about development of simple hyperplasia, this was very slight and not accompanied by cellular pleomorphism. The present results demonstrated that intravesical instillation of antineoplastic agents can cause a proliferative response and cytotoxicity after only short-term treatment and suggest that this chemotherapy could itself play a possible role in promotion of bladder carcinogenesis or cancer development.