Effect of dose on the induction of urothelial proliferation by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide and its relationship to bladder carcinogenesis in the rat.
The effect on urothelial proliferation of a urinary bladder carcinogen, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT), fed to male F344 rats at doses of 0.2, 0.1, 0.05, 0.01, 0.005 and 0.001% of diet for 4 or 10 weeks was evaluated by autoradiography, using [3H-methyl]thymidine, and by histopathology. At week 4, hyperplasia was induced in 10/11 and 6/11 rats given 0.2% and 0.1% FANFT, respectively. The dose-related increase of labeling index in the bladder epithelium was significant for the groups given 0.01% or higher doses of FANFT. At week 10, histopathologic lesions were observed in groups given 0.05% or higher doses of FANFT. This was accompanied by a significant increase in labeling index for these groups. The results are consistent with the long-term carcinogenicity studies conducted with the same dose levels of FANFT. The interrelationships between numbers of cells (hyperplasia), cell proliferation (labeling index) and cancer induction are discussed utilizing a computerized model of bladder carcinogenesis.
R
R
Hasegawa
S M
SM
Cohen
M
M
St John
M
M
Cano
L B
LB
Ellwein
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005200:FANFT / Q000633:toxicity*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013844:Thiazoles / Q000633:toxicity*; D013936:Thymidine / Q000378:metabolism; D001743:Urinary Bladder / Q000166:cytology* / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced*
D013844:Thiazoles; D005200:FANFT; D013936:Thymidine