Irreversibility of Low-Grade Superficial Rat Bladder Carcinomas1

The present investigation was conducted to determine: (a) whether the superficial papillary tumors developing in heterotopically transplanted bladders (HTBs) of rats after A/-methyl-/Vnitrosourea (MNU) initiation and subsequent weekly urine treat ment would regress when placed in a urine-free environment; (b) whether tumors would develop in HTBs if MNU initiation is not followed by further manipulation, such as instillation of urine or 2.1% NaCI solution; and (c) whether tumors would develop in HTBs if urine instillation is delayed for as many as 25 weeks after MNU initiation. The results indicate: (a) that low-grade superficial tumors, once developed, do not appear to regress in a urine-free environment; (b) that tumors develop in MNU-initiated bladders even if they receive no further treatment; and (c) that late institution of urine instillation to HTBs still effectively en hances MNU-initiated tumorigenesis. If the current observation is extrapolated to the human situation, our data suggest that low-grade superficial tumors are indeed neoplastic, and sponta neous regression cannot be expected by urinary diversion. It, however, might be effective in controlling progression of at least some of the early neoplastic lesions to overt cancer.