nefurthiazole and Urinary-Bladder-Neoplasms

Rats, mice and hamsters, which are susceptible to the bladder carcinogenesis by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT), and guinea pigs, which are not, were fed a diet containing 0.188% FANFT or 0.188% 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT) for 1 week and their urine was then examined for mutagenicity for S. typhimurium TA100. The mutagenicities of the urine of these species fed FANFT were approximately equal. Similarly, that of the urine of these species fed ANFT were also approximately equal. However, the urine from FANFT-fed animals was approximately 10 times as mutagenic as that from ANFT-fed animals. ANFT was detected only in the urine of rats, mice or hamsters fed FANFT. A positive correlation between the susceptibility toward bladder carcinogenesis by FANFT and urinary ANFT excretion was demonstrated, although the correlation between this susceptibility and urine mutagenicity was lacking.

Topics: Animals; Biotransformation; Carcinogens; Cricetinae; FANFT; Female; Guinea Pigs; Mesocricetus; Mice; Mutagenicity Tests; Mutagens; Mutation; Nitrofurans; Rats; Rats, Inbred Strains; Salmonella typhimurium; Species Specificity; Thiazoles; Urinary Bladder Neoplasms; Urine

Primary bladder tumors induced in Fischer 344 inbred rats by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide were transplanted in syngeneic rats by the intravesical, s.c., i.v., and orthotopic routes. Attempts were made to establish bladder cancer cell lines in vitro. No success was achieved in transplantation by either the s.c., i.v., or intravesical routes when primary tumor cells were transplanted as cell suspensions. Cell suspensions of primary tumors also failed to grow in culture. However, orthotopic implantation into the bladder submucosa gave 45% success. Tumor fragments obtained from either the primary tumor or its lung metastases resulted in 10.6 and 36% tumor takes, respectively, when implanted s.c. However, after one orthotopic passage in the bladder submucosa, the tumor cells injected as cell suspension grew s.c. in 14% and orthotopically in 79% of the animals. Tumor fragments obtained from orthotopic tumors and implanted s.c. resulted in 15% tumor takes. After the second orthotopic passage, tumor cells could be grown in cultures and orthotopically in 100% of animals. The technique of orthotopic implantation as well as the usefulness of this tumor model for bladder cancer studies are described.

Topics: Animals; Carcinogens; Neoplasm Transplantation; Neoplasms, Experimental; Nitrofurans; Rats; Rats, Inbred F344; Transplantation, Isogeneic; Urinary Bladder Neoplasms

We gave 102 male Fischer 344 rats (100 to 200 g) 0.2 per cent nitrofurylthiazolyl formamide (FANFT) diet for 14 weeks. Half of the animals underwent urinary diversion and half, sham operation. All animals resumed the FANFT diet. Half of each of the groups received four weekly i.p. injections of cyclophosphamide and the remainder received saline injections. The animals were sacrificed 12 weeks after diversion or sham operation. The incidences of tumor and tumor invasion were tabulated. Urinary diversion produced a greater effect in reducing progression of early neoplastic lesions to gross or microscopically invasive tumor than did systemic cyclophosphamide; however, an additive effect was noted when diversion and cyclophosphamide therapy were combined.

Topics: Animals; Body Weight; Carcinogens; Carcinoma, Papillary; Cyclophosphamide; Male; Neoplasms, Experimental; Nitrofurans; Organ Size; Rats; Thiazoles; Urinary Bladder; Urinary Bladder Neoplasms; Urinary Diversion