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Multistage carcinogenesis in the urinary bladder.

S M Cohen, R E Greenfield, L B Ellwein

    Environmental Health Perspectives
    |March 1, 1983
    PubMed
    Summary
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    Urinary bladder cancer development is a multi-step process. Cell proliferation and hyperplasia are key factors in carcinogenesis, as demonstrated by studies using N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) and promoters like sodium saccharin.

    Area of Science:

    • Oncology
    • Carcinogenesis Research
    • Urothelial Biology

    Background:

    • Urinary bladder cancer induction involves multiple exogenous and endogenous factors.
    • The classical initiation-promotion model is a framework for understanding this multi-stage process.

    Purpose of the Study:

    • To investigate the roles of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) as an initiator and sodium saccharin (SAC) or tryptophan as promoters in urinary bladder carcinogenesis.
    • To explore the influence of urine factors and cell proliferation on tumor development.
    • To develop a stochastic computer model for analyzing bladder carcinogenesis variables.

    Main Methods:

    • Utilized FANFT as an initiator and SAC or tryptophan as promoters in animal models.
    • Administered promoters at different time points relative to FANFT exposure.

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  • Investigated tumor induction in animals with pre-existing bladder mucosa proliferation (ulceration, pellet insertion, in utero).
  • Formulated a stochastic computer model based on carcinogenicity and tissue kinetic studies.

    • Main Results:

    • Tumor induction occurred when promoters were administered after FANFT initiation, regardless of timing.
    • No tumors formed if promoters were given without FANFT initiation.
    • SAC induced bladder tumors even without FANFT initiation in animals with rapidly proliferating bladder mucosa.
    • The computer model highlighted the significance of cell proliferation and hyperplasia in carcinogenesis.

    Conclusions:

    • Cell proliferation and hyperplasia are critical elements in urinary bladder carcinogenesis.
    • The timing of promoter exposure and the state of the bladder mucosa influence tumor development.
    • A stochastic model provides insights into the complex interplay of factors in bladder cancer induction.