URINARY-BLADDER CARCINOGENESIS

Urinary bladder carcinogenesis in rodents bears numerous similarities to the diseases in humans. In rats, the process progresses through the morphologic stages of simple hyperplasia, papillary and nodular hyper plasia, papilloma, noninvasive, and invasive carcinoma. In mice, the p athogenesis can be similar or can follow a sequence of marked dysplasi a with or without hyperplasia, leading to carcinoma in situ and ultima tely to high-grade invasive carcinoma. Although the papillary and nonp apillary diseases appear to be related in rodents and in humans, they are distinct morphologically, biologically, and molecularly. Numerous classes of genotoxic chemicals have been identified as bladder carcino gens in rodents, and some of these have also been identified as carcin ogenic in humans, most notably, aromatic amines, nitrosamines, and cyc lophosphamide. In contrast, nongenotoxic chemicals appear to be highly specific with respect to species, strain, diet, agent, dose, and mech anism. For some, it is unclear whether the results at high doses in ro dents can be extrapolated to low doses or to humans, e.g., chemicals t hat cause bladder cancer only at high doses related to the formation o f calculi. Numerous observations in rodents can assist in identifying possible mechanisms involved for these nongenotoxic chemicals and ther efore can be important for a rational evaluation of human risk.