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At least 19 recordsLinked to original sources
PubMed1983

Cellular changes in rat urinary bladder carcinomas induced by FANFT: a quantitative electron microscopic analysis.

Morphometric data of normal and neoplastic urinary bladder epithelia have been collected from the Fischer rat FANFT model. Sequential measurements of volumes, surface areas, and numerical densities of organelles, and where pertinent, cellular compartments have been made during FANFT carcinogenesis, utilizing standard point and intersection counting methods. The data show that neoplastic transformation of rat bladder epithelium, and progression of FANFT tumors are associated with increasing volume densities of cells, nuclei, microvilli, rough endoplasmic reticulum, and mitochondria, as well as with decreasing volume densities of the cytoplasmic matrix, fusiform vesicles, Golgi complex, and lysosomes. Surface densities of the plasma membrane (microvillar), nuclei, rough endoplasmic reticulum, as well as mitochondrial outer and inner membranes progressively increase while surface densities of non-microvillar plasma membrane, fusiform vesicles, and Golgi complex decrease with time. Smooth endoplasmic reticulum reaches its maximum volume and surface densities in tumors present 26 weeks after the initiation of FANFT feedings (26-F tumors). This may reflect the function of smooth endoplasmic reticulum as the site of detoxification of the carcinogen, noting that FANFT is metabolized by microsomal enzymes, and in this experiment is fed only for 26 weeks. The nuclear/cytoplasmic ratio is 1:4 in normal Fischer rat urothelium, 1:3 in 26-F and 43-F tumors, which are noninvasive, and 1:2 in 61-F, which are invasive tumors. The quantitative data correlate well with the changes in degree of differentiation of the tumors and with their biological behavior.

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PubMed1983

The influence of phenacetin or mechanical perforation on the development of renal pelvic and urinary bladder tumors in FANFT-induced urinary tract carcinogenesis.

The influence of 0.535% phenacetin in the diet or mechanical perforation of the renal pelvis and urinary bladder of male Sprague-Dawley rats in FANFT-induced urinary tract carcinogenesis was studied. The 151 rats were divided into 5 experimental and one control group. The rats were followed for up to 80 weeks. FANFT administered at 0.2% in the diet for 11 weeks resulted in a high incidence of urinary tract tumors particularly of the renal pelvis. Similar results were obtained by administration of 0.2% FANFT for 6 weeks followed by 0.535% phenacetin while FANFT for 6 weeks preceded or followed by mechanical perforation of the renal pelvis resulted in a significantly lower incidence of renal pelvic tumors. Phenacetin appeared to enhance the development of renal pelvic tumors in FANFT-induced urinary tract carcinogenesis. In contrast no effect of phenacetin on the urinary bladder could be detected.

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PubMed1987

Enhanced expression of Harvey-ras oncogene in FANFT-induced transitional cell carcinoma.

The level of mRNA expression and DNA structure of c-H-ras were examined in a transitional cell carcinoma (TCC) induced in C3H/He mice and Fisher rats by N-(4,5-nitro-2-furylthiazolyl)formamide (FANFT) and carried as serially transplanted tumors. Neither amplification nor gross rearrangements were detected by Southern analysis in the FANFT tumor. Increased expression of c-H-ras was detected by Northern and in situ hybridization in both the FANFT-induced mouse and rat TCC, as compared to normal urothelium. No expression of six other cellular oncogenes was detected in the tumor. It appears that the increase in H-ras expression in the FANFT tumor is specific to this oncogene and that increased expression of the H-ras gene may play a role in bladder carcinogenesis.

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PubMed1984

The Noble rat bladder cancer model. FANFT-induced tumors.

This laboratory unit has been working with the Nb rat prostate adenocarcinoma model for the last several years and has recently used this model system to study efficacy of various chemotherapeutic agents in FANFT-induced bladder carcinomas in this rat strain. The purpose of this project is to identify factors and chemotherapeutic agents that might be useful for treatment of human bladder carcinoma. It is proposed that the use of the Nb rat be utilized to develop a data base to advance understanding of the management of bladder carcinoma induced by FANFT ingestion in Nb rats. Conventional cytotoxic agents and new combination chemotherapy will be utilized intravesically and systemically.

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PubMed1982

Growth characteristics of N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT)-induced mouse bladder tumor lines in a human tumor stem cell assay.

Four N-[4-(5-nitro-2-furyl)-2-thiazolyl]-Formamide (FANFT)-induced mouse bladder tumor (MBT) lines were tested for their ability to form colonies in a tumor stem cell assay. Anticancer drug testing was done using this assay to determine whether reproducible colony survival curves could be be produced. All four cell lines produced colonies at 10--14 days, whether taken from culture or murine tumor. Cloning efficiencies ranged from 0.29% to 1.93% from culture and from 0.005% to 0.05% from the murine source. Growth characteristics were described. Cells from colonies were histologically similar to the original cells plated. A linear relationship existed between the number of cells plated and the number of colonies produced. In vitro drug studies were reproducible and correlated with in vivo data. Therefore, MBT lines can be used for in vitro drug testing in a tumor stem cell assay and may be useful in selecting active chemotherapeutic agents in the murine tumor model.

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PubMed1990

Oncogene expression of FANFT- or BBN-induced rat urothelial cells.

Proto-oncogene expression by cultured urothelial cells prepared from the bladders of male F344 rats that had been treated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT) or N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were examined. Although all of the cultured cells showed varying degrees of anchorage-independent growth, only 9 of them were transplantable into nude mice. A Northern blot technique was employed for the detection of proto-oncogene transcripts. The c-Ha-ras transcripts were detected in all the cultured urothelial cells prepared from the carcinogen-treated rats and in normal urothelial cells. However, the transcript levels were several-fold higher in the former than in normal cells. Increased expression of p21, as determined by immunohistochemical techniques, was also observed in all the original bladder tissues from which the cultures were derived. c-myc transcripts were detected in the cells from carcinogen-treated rats but not in the normal cells. The presence of myc product in hyperplastic urothelial lesions and carcinomas of original bladder tissues was confirmed by immunohistochemical methods. Transcripts of mos, erb B, Ki-ras, abl and src were not detected. Since increased expression of c-myc and c-Ha-ras were present in both transplantable and non-transplantable cell lines, and the expression of p21 occurs in preneoplastic cells, this suggests that elevated expression of these 2 genes may be an early genetic event during bladder carcinogenesis in the rat and further alteration of these 2 genes or mutation of additional genes may be required for the completion of malignant transformation.

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PubMed1983

The relationship of histamine H2 receptor-bearing suppressor cells with the growth and metastasis of FANFT-induced bladder cancer.

A poorly differentiated transitional cell carcinoma in C3H/He mice results from the oral ingestion of the urinary tract carcinogen FANFT. This model, designated MBT2, is readily transplantable into syngeneic animals and has proven to be very useful in the development of chemotherapy. Prior to the use of this model for the testing of potential immunotherapeutic strategies, we have attempted to characterize the immunobiology of this tumor line. We report that the primary growth of this tumor in the footpad and its metastasis to lung are correlated with the development of increased numbers of suppressor cells, characterized by the expression of a surface histamine H2 receptor. These cells are originally evident in spleen and become maximal approximately 4 weeks after tumor implantation. This is followed by the migration of these cells from spleen to peripheral blood, an event that parallels the growth and eventual metastasis of this implanted transitional cell carcinoma. These events may have important significance for the development of immunomodulating therapy against bladder cancer.

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PubMed1987

A dose response analysis of purpurin derivatives used as photosensitizers for the photodynamic treatment of transplantable FANFT induced urothelial tumors.

Rats engrafted with transplantable N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) induced urothelial tumors were treated with purpurin derivatives and red light (greater than 590 nm., 360 joules/cm.2). Treated and control tumors were harvested 12 days after treatment and dry weights compared. At doses of 5.0 micrograms./gm. and 2.5 micrograms./gm. body weight, the purpurins designated NT1 and NT2, when combined with light, caused statistically significant (p less than 0.02) tumor regression when compared to light shielded controls. At 1.0 micrograms./gm. body weight, NT1 and light also induced significant tumor regression (p less than 0.02). Purpurins, which have strong absorption bands above 650 nm. and can be synthesized with a high degree of purity, appear to have potential as photosensitizers for photodynamic therapy.

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PubMed1982

In vitro characterization of four N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) induced mouse bladder tumors.

Four longterm murine bladder tumor cell lines were established in vitro. The 4 lines were initiated from primary N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) induced murine bladder tumors arising in C3H/He mice. Each was maintained as a solid tumor in syngeneic mice for at least 30 generations before initiation in tissue culture. The cell lines MBT-2, MBT-8, MBT-409 and MBT-683, have been subcultured over 75 times in vitro for 18 months. They are all epithelial, grow in islands on plastic Petri dishes before confluent growth and form colonies in soft agar suspension culture. Morphologic studies indicate that all 4 lines have epithelial characteristics and karyotypic studies indicate that all lines have polyploidy and marker chromosomes. Population doubling times range from 10 to 26 hours and are consistent for each line.

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PubMed1979

Intravesical thio-tepa: a study of 3H-thymidine uptake in normal urothelium and FANFT-induced tumors in rats.

Treatment of superficial low-grade bladder cancer often incorporates intravesical instillations of the alkylating agent thio-TEPA. Current dosages and administration schedules are empiric inasmuch as cytokinetic data are sparse. The FANFT-induced bladder rat tumor model closely approximates human bladder cancer. This study measuring 3H-thymidine uptake identified peaks of maximal synthetic activity at 3 and 9 days after thio-TEPA exposure in both normal and neoplastic urothelium. Thus, repeat instillation at these intervals may improve cytotoxicity and overall response rate.

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PubMed1975

Failure of ascorbic acid to inhibit FANFT-induced bladder cancer.

L-ascorbic acid has been shown to reduce the elevated level of urinary chemiluminescence found in patients with bladder cancer. Thus, it has been suggested that vitamin C might be efficacious in bladder tumor prophylaxis. However, there is no clinical evidence to support this thesis. We evaluated whether L-ascorbic acid given concomitantly with the urinary carcinogen FANFT was capable of reducing the incidence of subsequent bladder tumors. No inhibitory effect was observed. Unless evidence is obtained demonstrating bladder tumor prevention by L-ascorbic acid its routine administration to patients with bladder cancer is not indicated.

Animals↗
PubMed1985

Quantitative measurements of humoral immune response in mice to a FANFT induced bladder tumor.

Using unfixed mouse bladder tumor cells (MBT) as target cells and a modified avidin-biotin-complex (ABC) method made it possible to detect a humoral immune response in C3H mice with growing MBT tumors. The rise of the serum levels is significant (p less than 0.005) when compared to control animals and correlates with the tumor size. Mice with recurrences after surgical removal of the primary tumor had significantly (p less than 0.05) higher serum values than animals without recurrence. Purulent or granulomatous inflammatory changes, muscle necrosis, growth of a lymphoma or an ovarian carcinoma did not significantly change the results (p less than 0.05). Injection of myeloma cells from a different strain of mice caused a minimal, but significant increase in the values when compared to controls (p less than 0.0001). However, the slope of the curve differed significantly (p less than 0.05) from that in mice with MBT tumors. Irradiated MBT cells or Corynebacterium parvum used as immunomodulators significantly increased the serum values (p less than 0.001). In the presence of a growing MBT tumor, however, the immunomodulation did not substantially falsify the results. The serum values were related to the corresponding tumor sizes.

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PubMed1990

Hemodynamic effect of the metallopurpurin SnET2 and light on transplantable FANFT induced bladder tumor.

Changes in blood flow to transplantable N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide induced bladder tumors growing subcutaneously in the flanks of Fischer CDF (F344/CrlBR) rats were measured after photodynamic therapy with the photosensitizer tin (II) etiopurpurin dichloride using the radioactive microsphere technique. As with the other photosensitizers, hematoporphyrin derivative and chloroaluminum tetrasulfophtalocyanine, tin (II) etiopurpurin dichloride and light caused a rapid decrease in tumor blood flow in this tumor model. The decrease in blood flow occurred whether the vehicle for photosensitizer delivery was an emulsion or a liposome. Systemic heparinization of animals prior to light treatment did not alter changes in tumor blood flow.

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PubMed1979

Intercellular junctions in FANFT-induced carcinomas of rat urinary bladder in tissue culture: in situ thin-section, freeze-fracture, and scanning electron microscopy studies.

This paper describes a set of simple methods for comparative light and electron microscopy studies on tissue cultured tumour cells derived from both noninvasive and invasive carcinogen-induced rat urinary bladder carcinomas. Cells are grown on Thermanox plastic coverslips and fixed in situ. Each plastic coverslip is then divided with scissors into four parts: the first is processed for light microscopy, the second for thin-section electron microscopy, the third for freeze-fracture electron microscopy, and the fourth for scanning electron microscopy. In some experiments, portions of the culture which have first been examined by light microscopy are subsequently prepared for electron microscopy. In this way, the culture conditions are kept constant and comparison of structural features (i.e. intercellular junctions) by several preparative techniques is possible. Noninvasive and invasive rat bladder tumour cells, characterized by numerous pleomorphic microvilli, have normal zonulae occludentes at the apices of lateral surfaces of tumour cells in all cultures. In some areas of invasive tumour cells, occludens junctions are focally attenuated, consisting of only one or two strands, and occasionally the strands are discontinuous. Gap junctions, type PF-1, as well as numerous demosomes are present in all cell lines. Thus, intercellular junctions in noninvasive and invasive rate bladder epithelial cell lines bear a striking resemblance to those previously described in the comparable solid primary tumours. These culture systems may be useful for studying factors which influence the formation of intercellular junctions during malignant transformation.

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