Multi-stage carcinogenesis in the urinary bladder

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Sodium saccharin has been shown to be a promoting substance for urinary bladder carcinogenesis in the rat following initiation with N-methyl-N-nitrosourea, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT), or N-butyl-N-(4-hydroxybutyl)nitrosamine. It has been shown to have many of the properties of promoting substances in other animal models, such as the mouse skin; it lacks mutagenic activity, induces hyperplasia in the target tissue, and does not bind to DNA. It has recently been demonstrated to be co-carcinogenic for the rat bladder. It has also been shown that the administration of sodium saccharin during the regenerative hyperplasia observed after freeze ulceration or cyclophosphamide administration resulted in the induction of bladder tumours, even without pre-initiation with FANFT or other known initiating substances. This model appears to be analogous to the administration of sodium saccharin to animals with a rapidly proliferating bladder mucosa as occurs in utero during the two-generation carcinogenesis experiments and in the pellet-insertion experiments in which a cholesterol pellet containing sodium saccharin is inserted into the bladder. To enhance our understanding of the complex interaction of the many variables involved in two-stage bladder carcinogenesis, a stochastic model has been formulated based on long-term carcinogenicity and in vivo tissue kinetic studies. This model indicates the importance of cell proliferation and the development of hyperplasia in carcinogenesis.

Original languageEnglish (US)
Pages (from-to)521-528
Number of pages8
JournalFood and Chemical Toxicology
Volume23
Issue number4-5
DOIs
StatePublished - Jan 1 1985

Fingerprint

Saccharin
saccharin
bladder
carcinogenesis
FANFT
Carcinogenesis
Urinary Bladder
hyperplasia
sodium
Hyperplasia
Rats
Animals
Butylhydroxybutylnitrosamine
pellets
Tissue
Methylnitrosourea
N-methyl-N-nitrosourea
Cell proliferation
Stochastic models
nitrosamines

ASJC Scopus subject areas

  • Food Science
  • Toxicology

Cite this

Multi-stage carcinogenesis in the urinary bladder. / Cohen, Samuel Monroe.

In: Food and Chemical Toxicology, Vol. 23, No. 4-5, 01.01.1985, p. 521-528.

Research output: Contribution to journalArticle

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