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Urinary bladder carcinogenesis

S M Cohen1

  • 1University of Nebraska Medical Center, Department of Pathology and Microbiology, Omaha 68198-3135, USA.

Toxicologic Pathology
|March 21, 1998
PubMed
Summary
This summary is machine-generated.

Rodent urinary bladder cancer models offer insights into human disease, distinguishing between genotoxic and nongenotoxic carcinogens. Understanding these mechanisms aids in evaluating human cancer risk.

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Area of Science:

  • Toxicology
  • Carcinogenesis
  • Comparative Pathology

Background:

  • Urinary bladder carcinogenesis in rodents shares similarities with human disease progression.
  • Rodent models exhibit distinct morphologic stages, including hyperplasia, papilloma, and carcinoma.
  • Papillary and nonpapillary bladder diseases in rodents and humans are morphologically, biologically, and molecularly distinct.

Purpose of the Study:

  • To compare urinary bladder carcinogenesis in rodents and humans.
  • To identify genotoxic and nongenotoxic chemical carcinogens relevant to both species.
  • To evaluate the utility of rodent models for assessing human cancer risk.

Main Methods:

  • Review of existing literature on rodent and human bladder cancer.
  • Classification of bladder carcinogens as genotoxic or nongenotoxic.

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  • Analysis of species-specific and dose-dependent mechanisms of carcinogenesis.

    • Main Results:

    • Genotoxic carcinogens like aromatic amines, nitrosamines, and cyclophosphamide are identified in both rodents and humans.
    • Nongenotoxic carcinogen mechanisms are highly specific to species, strain, diet, agent, dose, and mechanism.
    • High-dose rodent studies involving calculi formation present challenges for human risk extrapolation.

    Conclusions:

    • Rodent models are valuable for understanding bladder cancer mechanisms, particularly for nongenotoxic agents.
    • Comparative analysis of genotoxic and nongenotoxic carcinogens informs human risk assessment.
    • Further research on high-dose rodent findings is needed for accurate extrapolation to low-dose human exposure scenarios.