TY - JOUR
T1 - Multi-stage carcinogenesis in the urinary bladder
AU - Cohen, S. M.
N1 - Funding Information:
Acknowledgements--I gratefully acknowledge the assistance of Jan Leemkuil in the preparation of this manuscript and the numerous colleagues who have contributed to the work described in this review. The work reported in this manuscript from my laboratory is supported in part by USPHS grants CA32313, CA28015, and CA32513 from the National Cancer Institute, the latter two through the National Bladder Cancer Project.
PY - 1985
Y1 - 1985
N2 - 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.
AB - 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.
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U2 - 10.1016/0278-6915(85)90146-2
DO - 10.1016/0278-6915(85)90146-2
M3 - Article
C2 - 4040099
AN - SCOPUS:0021805838
VL - 23
SP - 521
EP - 528
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
SN - 0278-6915
IS - 4-5
ER -