Disease relevance of FANFT

• Rats fed FANFT for 10 weeks and then the control diet developed hyperplastic epithelial lesions and carcinomas by week 52, whereas those fed FANFT for 6 weeks had normal bladders through 52 weeks [1].
• FANFT administration increased the incidences of mesothelioma of the peritoneum and thyroid tumors [2].
• PB significantly increased the incidence of transitional cell carcinoma of the bladder of the rats that had been treated with FANFT (P = 0.027) [3].
• By the 50th week the rats fed FANFT for 8 weeks all had moderate to marked hyperplasia, but the rats fed FANFT for 10 weeks had transitional cell tumors, one of which was invasive through the entire thickness of the bladder wall [4].
• Of 26 rats fed SAC for 100 weeks after FANFT, two developed papillomas, and five developed carcinomas (p less than 0.03) [5].

High impact information on FANFT

• Numerical but not structural changes of chromosomes were significantly greater in the FANFT group than in the BBN group [6].
• There is substantial evidence that N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) is deformylated to 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT) in the process of FANFT-induced bladder cancer [7].
• Neither aspirin nor probenecid altered the urinary excretion or half-life of FANFT or ANFT [7].
• The carcinogen N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (CAS: 24554-26-5) was fed to male and female CD-1 mice in the diet as a positive control [8].
• The epithelial lesions present after 6 and 10 weeks of FANFT feeding also regressed and the mucosa returned to normal as observed by light microscopy [1].

Chemical compound and disease context of FANFT

• Administration of FANFT to vitamin A-deficient rats appeared to accelerate the carcinogenic process, with earlier appearance of urinary bladder tumors and the development of ureteral and renal pelvic carcinomas [9].
• N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) administration to rats followed by sodium saccharin results in transitional cell carcinomas of the bladder, of which 24% harbor an activated H-ras gene [10].
• Nitrofurantoin caused in vitro growth inhibition of a FANFT-induced murine bladder tumor (MBT2) and a human transitional cell carcinoma cell line (GIBB) in concentrations of 125 microM, 250 microM and 500 microM [11].
• Thirty-two animals treated with FANFT and 33 treated with FANFT + sutures also received supplements to their drinking water throughout the experiment of the sulfhydryl-reducing agent N-acetylcysteine (500 mg./kg. body weight/day) [12].
• The relative toxicities were as follows: FANFT greater than AF2 greater than ANFT greather than furazolidone greater than furagin greater than nitrofurantoin greater than nitrofurazone greater than methylnitrofuroate greater than nitrofuroic acid [13].

Biological context of FANFT

• The biotransformation of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT), a potent urinary bladder carcinogen, was studied in mice [14].
• Other inhibitor and substrate specificity studies suggest that FANFT was not metabolized by nitroreductase, xanthine oxidase, lipoxygenase, lipid peroxidation, or mixed-function oxidases [15].
• Oncogene expression of FANFT- or BBN-induced rat urothelial cells [16].
• The results showed no mutation within the examined DNA sequences, indicating that neu oncogene is not activated by a point mutation in the transmembrane domain in urinary bladder carcinomas induced by BBN, FANFT or MNU [17].
• FANFT-induced cell proliferation in the bladder was significantly suppressed by aspirin co-administration after 4 weeks but not after 12 weeks [18].

Anatomical context of FANFT

• Hyperplastic mucosa with pleomorphic microvilli was also observed at 52 weeks in rats fed 0.1% and 0.05% FANFT [19].
• The present study was designed to evaluate whether chronic urinary tract infection could enhance tumor development in FANFT-induced urinary tract carcinogenesis [20].
• Rats fed FANFT for 6 weeks show regression of the moderately hyperplastic epithelium to normal within 4 weeks after being placed on control diet which persists through 50 weeks [4].
• One wk after completion of FANFT administration, a suspension of heat-killed E. coli (06K13H1) was injected into the bladder through the urethra [20].
• FANFT alone had no effect on hepatic cytosol or microsomal nitroreductase activity but increased hepatic and blood acid-soluble thiol content [21].

Associations of FANFT with other chemical compounds

• However, the hyperplastic effects induced in the bladder epithelium by saccharin without prior FANFT administration were inhibited by coadministration with aspirin [22].
• N-[4-(5-Nitro-2-furyl)-2-thiazolyl]formamide (FANFT), a potent urinary bladder carcinogen, is metabolically activated in vitro by a variety of enzyme systems including aerobic cooxidation by prostaglandin H synthase which is present in the rat bladder mucosa [23].
• Both chemicals significantly increased the incidence of bladder tumors following FANFT feeding compared to six weeks of FANFT feeding followed by control diet, and the results were similar whether saccharin or tryptophan feeding was started immediately after FANFT feeding was concluded or after a six-week delay [24].
• The effects of aspirin on N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT) -induced urinary bladder lesions, endogenous bladder prostaglandin E2 synthesis, and the metabolism of FANFT by bladder epithelial microsomes were examined [25].
• The effects of allopurinol on the induction of bladder cancer by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT), excretion of urinary tryptophan metabolites, hepatic nitroreductase activity, and the acid-soluble thiol content of liver and blood in weanling female Fischer rats were investigated [21].

Gene context of FANFT

• Mice given FANFT p.o. demonstrated a significant increase over controls in ornithine decarboxylase activity within 12 hr, followed by a gradual decline to control levels by 72 hr [26].
• Further investigations using immunohistochemical staining with a different pan-reactive p21 monoclonal antibody (Cetus Corporation) specific for this method, however, showed two groups of cells from FANFT-induced rat bladder tumors had enhanced immunoreactivity [10].
• Screening by Western blotting revealed no enhanced levels of p21ras in ANFT-transformed cells nor in cells established in culture from FANFT-induced rat bladder carcinomas [10].
• With monoclonal antibody PAb421 (which detects mutant and wild-type p53), p53 antigen was also detected in cells from F542, a bladder tumor induced by FANFT in which no p53 mutations were found [27].
• Using a standard clonogenic assay and the AY-27 FANFT tumor line, photoactivation of CDS1 was shown to be cytotoxic [28].

Analytical, diagnostic and therapeutic context of FANFT

• Urine specimens obtained periodically from weanling male F344 rats fed 0.2% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) for 25 weeks followed by control diet for an additional 35 weeks, were examined by light microscopy (LM) and scanning electron microscopy (SEM) [29].
• Control groups consisted of rats that received tap water with or without prior administration of FANFT [2].
• Histological appearance and biological behavior of tumor isografts closely resembled those of the original FANFT tumors [30].
• Using low (less than 10) and high (greater than 80) passages of these cell strains, tumorigenicity experiments in syngeneic rats showed that the normal in vivo progression of FANFT tumors was interrupted by the isolation of carcinoma cells to cell culture [30].
• 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 [31].

References