Biomedical subjects

T Masui

Publications and source records attributed to T Masui.

At least 91 records · Page 5Linked to original sources

PubMed1992

Effect of cilazapril on regional left ventricular wall thickness and chamber dimension following acute myocardial infarction: in vivo assessment using MRI.

The primary goal of the current study was to assess in situ, using magnetic resonance imaging, the effect of a new angiotensin-converting enzyme inhibitor, cilazapril, in reducing left ventricular remodeling after acute myocardial infarction. Three groups of animals were investigated: (1) sham-operated rats (n = 19); (2) infarcted rats receiving no treatment (n = 23); and (3) infarcted rats receiving cilazapril (100 mg/L drinking water, n = 20). Treatment with cilazapril began on the third day postocclusion and continued for 3 to 4 months. Myocardial infarction was produced by ligation of the left coronary artery, and electrocardiographic (ECG)-gated short-axis images were acquired 3 to 4 months later. Sham-operated animals were subjected to the same procedure but the left coronary artery was not ligated. From the image acquired in the middle of the left ventricle (equatorial slice), left ventricular wall thicknesses, chamber diameters, and surface area measurements of the cavities were determined. At autopsy examination, infarct size and tissue water content were determined. The results demonstrate that magnetic resonance imaging has the potential to assess in situ the alterations of left ventricular dimensions and mass after acute myocardial infarction and can be used to document the influence of therapeutic interventions. Cilazapril provided protection against the deleterious remodeling changes such as ventricular dilation and wall thinning consequent to acute myocardial infarction.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1992

Pathological markers for non-genotoxic agent-associated carcinogenesis.

A variety of positive or negative enzyme altered foci have been proposed as preneoplastic marker lesions in the rat liver. Frozen sections are required in some cases. We have compared the suitability of various histochemically or immunohistochemically demonstrated markers and concluded that immunohistochemically-stained glutathione S-transferase placental form (GST-P) positive foci are particularly useful for practical application in risk assessment. Advantages include ease of quantitative foci analysis on a number of samples since acetone or formalin-fixed paraffin blocks can be used and clear contrast of foci against the surrounding liver tissue facilitates recognition. We have established a liver medium-term bioassay model of 8 weeks' duration using diethylnitrosamine as an initiator and GST-P positive foci as the endpoint lesions. At present, 58 non-genotoxic chemicals for which carcinogenicity data are available have been examined and many carcinogenic agents, mostly liver carcinogens, have been satisfactorily detected as having carcinogenic potential. Exceptional examples are two peroxisome proliferators, clofibrate and DEHP. For these chemical, several peroxisomal enzymes such as catalase and enoyl CoA hydratase have been tested as markers.

Animals↗

PubMed1992

Absence of ras oncogene activation in rat urinary bladder carcinomas induced by N-methyl-N-nitrosourea or N-butyl-N-(4-hydroxybutyl)nitrosamine.

Previously, we demonstrated point mutations of the H-ras gene in N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT)-induced rat urinary bladder carcinomas. In this study, ras oncogene activation was examined in urinary bladder carcinomas induced by N-(4-hydroxybutyl)nitrosamine (BBN) or N-methyl-N-nitrosourea (MNU) administration followed by uracil treatment. In the first experiment, MNU (20 mg/kg body wt) was i.p. injected into 11 male F344 rats twice a week for 4 weeks, followed by feeding 3% uracil for 20 weeks (MNU/uracil group). Ten rats were given only 3% uracil without MNU pretreatment. In the second experiment, 20 male F344 rats were given 0.05% BBN in the drinking water for 4 weeks, then fed 3% uracil for 20 weeks (BBN/uracil group). Another 20 rats were fed 3% uracil without the BBN pretreatment. Transitional cell carcinomas were induced in the urinary bladder of all rats in the MNU/uracil and BBN/uracil groups. Papillomas and hyperplasias were present in the rats given uracil without prior BBN or MNU. DNA and protein were extracted from the tumors (MNU/uracil or BBN/uracil groups) or from the scraped bladder epithelium (uracil alone groups). Sequences around codons 12, 13 and 61 of H-, K- and N-ras genes were examined by direct sequencing after polymerase chain reaction, and p21 was examined by Western blotting. No mutation was found within the examined sequences and p21 showed no changes in mobility. There was no difference in the level of p21 expression between rats treated with MNU/uracil or BBN/uracil compared to corresponding uracil alone groups. These results indicate that the ras oncogene was not activated in urinary bladder carcinomas induced by BBN or MNU in combination with uracil treatment, in contrast to previous findings with FANFT.

Animals↗

PubMed1992

Ras involvement in cells transformed with 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT) in vitro and with N-[4-(5-nitro-2-furyl)-2-thiazoyl]formamide in vivo.

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. Since 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT) is the mutagenic and carcinogenic metabolite of FANFT in vivo, we wished to examine ras activation in in vitro ANFT-transformed rat bladder epithelial cells as well as four cell lines established in culture from in vivo FANFT-induced rat bladder tumors. 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. 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. Apart from this, p21ras expression of most of the cells groups varied little from the controls. We examined the reported hot spots (exons 1 and 2) of each of the ras genes (H-, K- and N-ras) by direct sequencing of amplified DNA. No mutations were present. We conclude, therefore, that ANFT transformation of primary rat bladder epithelial cells in vitro may not in this case be mediated by ras activation, although this is difficult to determine since others have observed that optimal culture conditions can select for certain populations of cells without ras activation.

Animals↗

PubMed1992

Dose dependence of N-hydroxy-3,2'-dimethyl-4-aminobiphenyl-induced rat prostate carcinogenesis.

Groups of F344 rats were administered biweekly intraperitoneal injections of N-hydroxy-3,2'-dimethyl-4-aminobiphenyl (N-OH-DMAB) at a dose of 5, 10 or 20 mg/kg body weight or DMAB, the parent compound, at a dose of 25 mg/kg body weight, for a total of 10 times. Prostate carcinomas in the ventral lobe developed in a N-OH-DMAB dose-dependent manner (0, 17.6 and 66.7%, respectively) with limited tumor yields in other organs. Although intraperitoneal administration of DMAB was similarly found to induce prostate tumors, it also caused severe chemical peritonitis, which resulted in a high mortality. The present data confirmed that intraperitoneal administration of N-OH-DMAB provides a relatively specific induction method for models of prostate carcinogenesis.

Aminobiphenyl Compounds↗

PubMed1992

Constrictive pericarditis and restrictive cardiomyopathy: evaluation with MR imaging.

Twenty-nine patients who were referred with the possible diagnosis of constrictive pericarditis underwent electrocardiographically gated transverse spin-echo magnetic resonance (MR) imaging to determine the accuracy of spin-echo MR imaging for the diagnosis of constrictive pericarditis and to compare the morphologic features of constrictive pericarditis with those of restrictive cardiomyopathy as seen on spin-echo MR images. Constrictive pericarditis was verified by means of surgery and/or catheterization in 17 patients. The sensitivity, specificity, and accuracy of MR imaging in the diagnosis of constrictive pericarditis were 88%, 100%, and 93%, respectively. Thickened pericardium was observed in 88% of patients with proved constrictive pericarditis. Pericardial thickening was not identified in patients with restrictive myocarditis (n = 4). The most frequent site of pericardial thickening was over the right ventricle. In constrictive pericarditis, the signal intensity of the thickened pericardium was similar or decreased compared with that of the myocardium. Indirect findings of impaired right ventricular diastolic filling (eg, dilatation of the inferior vena cava and right atrium) were identified in constrictive pericarditis and restrictive cardiomyopathy. MR imaging can serve as a noninvasive examination for the definitive diagnosis of constrictive pericarditis and can help distinguish between constrictive pericarditis and restrictive cardiomyopathy on the basis of pericardial thickness.

Cardiomyopathy, Restrictive↗

PubMed1992

Popliteal and tibioperoneal arteries: feasibility of two-dimensional time-of-flight MR angiography and phase velocity mapping.

To assess the feasibility of using magnetic resonance (MR) angiography and velocity-encoded cine MR imaging to evaluate morphology and function in the popliteal and tibioperoneal arteries, the profiles of blood flow velocity measured with velocity-encoded cine MR were compared with those measured with color-coded sonography. Two-dimensional time-of-flight MR angiography was performed in the popliteal and tibioperoneal arteries of 10 healthy subjects; velocity-encoded cine MR and color-coded sonography were performed above and below the trifurcation. The velocity waveforms acquired with velocity-encoded cine MR and color-coded sonography correlated well and showed a typical triphasic pattern. At peak systole in the popliteal artery, spatial maximum and spatial mean velocities measured with velocity-encoded cine MR were 42.29 cm/sec +/- 9.55 (standard deviation) and 27.7 cm/sec +/- 5.8, respectively; the peak velocity measured with color-coded sonography was 44.2 cm/sec +/- 12.3. It is concluded that use of both MR angiography and velocity-encoded cine MR should be considered for identification of arterial stenoses and assessment of the hemodynamic importance of peripheral vascular stenoses.

Adult↗

PubMed1992

Reperfusion and irreversible myocardial injury: identification with a nonionic MR imaging contrast medium.

The potential of a new nonionic gadolinium complex--gadodiamide injection--to (a) allow distinction between reperfused and occlusive infarction and (b) enable differentiation between reperfused reversible and irreversible myocardial injury was investigated. Three groups of rats were used: 10 with reversibly reperfused myocardial injury, 10 with irreversibly reperfused injury, and 10 with occlusive infarction. Before administration of contrast material, there was no significant difference in signal intensity between normal and injured regions on T1-weighted images. After administration of gadodiamide injection (0.2 mmol/kg), the reversibly injured myocardium was indistinguishable from normal myocardium, while the reperfused irreversibly injured zone showed prominent and homogeneous enhancement. Occlusive infarcts showed three zones of differential enhancement consisting of normal, periinfarction, and infarction regions. Gadodiamide injection provides differential enhancement in reversibly reperfused, irreversibly reperfused, and occlusive infarcts. Thus, it may be useful as a marker of reperfusion and extent of infarction after thrombolytic therapy.

Animals↗

PubMed1992

Pulmonary hypertension: pulmonary flow quantification and flow profile analysis with velocity-encoded cine MR imaging.

Velocity-encoded cine magnetic resonance (MR) imaging provides two-dimensional velocity maps of a cross-sectional area of a vessel. Pulmonary flow and flow patterns in the main pulmonary artery were analyzed with velocity-encoded cine MR imaging and Doppler echocardiography in 10 patients with pulmonary hypertension (PH), one patient with a dilated main pulmonary artery, and 10 healthy subjects, and these findings were compared. Peak systolic velocity measured with velocity-encoded cine MR imaging was similar to that measured with Doppler echocardiography in healthy subjects and in patients with PH. Velocity-encoded cine MR imaging demonstrated substantial differences in velocity across the vascular lumen in PH. The flow pattern in healthy subjects was different than that in patients with PH; the latter had lower peak systolic velocity and greater retrograde flow after middle to late systole. The retrograde flow observed in patients with PH reflected hemodynamic events, since it was inversely proportional to pulmonary flow volume and directly proportional to pulmonary resistance and cross-sectional area of the vessel. Velocity-encoded cine MR imaging demonstrates an inhomogeneous flow profile in PH and may serve as a noninvasive method to estimate pulmonary vascular resistance.

Adult↗

PubMed1992

[Cell culture and its application. Culture systems of normal human epithelial cells and their potential applications in cancer research].

In cancer research, it is essential to understand the differences of normal and carcinoma cells. To date there are not many studies of normal human epithelial cells because of difficulties in obtaining human materials and culturing them. After Peehl and Ham developed a low calcium medium which does not require feeder cells, the culture of normal human epithelial cells became relatively easy. In this paper, I will describe and compare different culture methods for normal human epithelial cells (mainly keratinocyte culture systems). We also present establishment processes of normal human ectocervical epithelial cell culture system that is dramatically improved by a combination of serum supplemented high-calcium and serum-free low-calcium media according to changes of a physiological state of the cells by passages. This suggest that we have to be aware of changes of cells in responses and use them in developing culture systems. I will also describe a study of mouse epidermal keratinocyte culture system and discuss the use of normal human epithelial cell system in screening potential chemotherapy reagents. In the study normal epithelial cells inhibit growth of initiated cells and this inhibition can be modified by tumor promoters and their inhibitors.

Calcium↗

PubMed1991

H-ras mutations in rat urinary bladder carcinomas induced by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide and sodium saccharin, sodium ascorbate, or related salts.

Male F344 rats were fed 0.2% N-[4-(5-nitro-2-furyl)-2-thiazoly]formamide for 6 weeks and then fed 3% or 5% sodium saccharin, 5% sodium ascorbate, 3.12% calcium saccharin, 1.34% sodium chloride, 5.2% calcium saccharin plus 1.34% sodium chloride, or basal diet alone for 72 weeks. Protein and DNA were extracted from 89 bladder tumors [87 transitional cell carcinomas (TCC), 1 papilloma, and 1 sarcoma] from 86 rats p21 expression was examined by Western blotting using a monoclonal antibody against p21 (NCC-RAS-004). H-ras mutations in exons 1 and 2 were examined by direct sequencing of DNA amplified by polymerase chain reaction. Sequencing results demonstrated mutations at codon 61 (CAA to CGA in 15 TCCs; CAA to CTA in 2 TCCs), at codon 12 (GGA to TGG in 1 TCC), and at codon 13 (GGC to GTC in 3 TCCs). Mutations at codon 61 were confirmed by faster mobility of the p21 band in Western blots. The level of p21 expression varied among samples, but many TCCs appeared to express more p21 than controls. The overall incidence of H-ras mutations was 24.4% (21 of 86 rats). The type of chemical used for the promoting phase had essentially no effect on H-ras mutation, suggesting that the effects observed were related to FANFT administration. The frequency of H-ras mutation in each group was negatively related to the incidence of carcinoma (r = -0.85; P less than 0.01). Two groups of tumors (with or without the mutated ras gene) were compared for tumor size (reflected by the bladder weight), histological grading, and the presence of invasion. The size of tumors with mutated ras was significantly smaller than those without mutated ras. There was no difference in the histological grading between the two groups. Although not statistically significant, histological invasion was more frequently observed in tumors with mutated ras (14.3%) than in tumors without mutation (3.1%).

Animals↗

PubMed1991

Comparative bladder tumor promoting activity of sodium saccharin, sodium ascorbate, related acids, and calcium salts in rats.

Sodium saccharin and sodium ascorbate are known to promote urinary bladder carcinogenesis in rats following initiation with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) or N-butyl-N-(4-hydroxybutyl) nitrosamine. Sodium salts of other organic acids have also been shown to be bladder tumor promoters. In addition, these substances increase urothelial proliferation in short term assays in rats when fed at high doses. When they have been tested, the acid forms of these salts are without either promoting or cell proliferative inducing activity. The following experiment was designed to compare the tumor promoting activity of various forms of saccharin and to evaluate the role in promotion of urinary sodium, calcium, and pH as well as other factors. Twenty groups of 40 male F344 rats, 5 weeks of age, were fed either FANFT or control diet during a 6-week initiation phase followed by feeding of a test compound for 72 weeks in the second phase. The chemicals were administered to the first 18 groups in Agway Prolab 3200 diet and the last 2 groups were fed NIH-07 diet. The treatments were as follows: (a) FANFT----5% sodium saccharin (NaS); (b) FANFT----3% NaS; (c) FANFT----5.2% calcium saccharin (CaS); (d) FANFT----3.12% CaS; (e) FANFT----4.21% acid saccharin (S); (f) FANFT----2.53% S; (g) FANFT----5% sodium ascorbate; (h) FANFT----4.44% ascorbic acid; (i) FANFT----5% NaS plus 1.15% CaCO3; (j) FANFT----5.2% CaS plus 1.34% NaCl; (k) FANFT----5% NaS plus 1.23% NH4Cl; (l) FANFT----1.15% CaCO3; (m) FANFT----1.34% NaCl; (n) FANFT----control; (o) control----5% NaS; (p) control----5.2% CaS; (q) control----4.21% S; (r) Control----control; (s) FANFT----5% NaS (NIH-07 diet); (t) FANFT----control (NIH-07 diet). NaS, CaS and S without prior FANFT administration were without tumorigenic activity. NaS was found to have tumor promoting activity, showing a positive response at the 5 and 3% dose levels, with significantly greater activity at the higher dose. CaS had slight tumor promoting activity but without a dose response, and S showed no tumor promoting activity. In addition, NaCl showed weak tumor promoting activity, but CaCO3 was without activity. NH4Cl completely inhibited the tumor promoting activity of NaS when concurrently administered with it. NaCl administered with CaS or CaCO3 administered with NaS showed activity similar to that of NaS. Sodium ascorbate was also shown to have tumor promoting activity, with slightly less activity than NaS. Ascorbic acid showed no tumor promoting activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Lack of bladder tumor promoting activity in rats fed sodium saccharin in AIN-76A diet.

Sodium saccharin (NaSac) fed as 5% of Prolab diet promotes bladder tumor carcinogenesis in male F344 rats initiated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) fed as 0.2% of the diet for 4 weeks. NaSac also increases urothelial proliferation if fed for short periods in Prolab diet, but no increased proliferation is seen if it is fed for up to 10 weeks in AIN-76A semisynthetic diet, even at levels as high as 7.5% of the diet. To determine whether NaSac as part of an AIN-76A diet has promoting activity, groups of approximately 30 male, 5-week-old F344 rats were fed AIN-76A diet containing (a) 0.2% FANFT for 4 weeks followed by 5% NaSac for 100 weeks; (b) 0.2% FANFT followed by control diet; or (c) control diet followed by 5% NaSac. Bladder tumor incidences were 10, 23, and 0%, respectively. When fed in Prolab diet, 0.2% FANFT for 4 weeks followed by NaSac or control diet for 100 weeks resulted in bladder tumor incidences of 40 and 17%, respectively. Groups of rats fed 0.1 or 0.2% FANFT for 1 or 2 weeks followed by 5% NaSac or control diet for 100 weeks had bladder tumor incidences of 0 to 7%. These data demonstrate that NaSac does not promote bladder cancer in male rats if fed in AIN-76A diet. Other studies suggest that this is due to the low urinary pH in rats fed AIN-76A diet.

Animals↗

PubMed1991

Assessment of right ventricular diastolic and systolic function in patients with dilated cardiomyopathy using cine magnetic resonance imaging.

Cine magnetic resonance imaging (MRI) can provide clear endocardial margins of the entire right ventricle, and Simpson's algorithm can be applied to obtain the volumes at multiple phases of the cardiac cycle. Time-volume curves of the right ventricle were obtained by using cine MRI in 10 patients with dilated cardiomyopathy (DCM) and eight normal volunteers to assess right ventricular function. There were no significant differences in volumes and ejection fraction of the right ventricle between the group with DCM and the normal group. In the group with DCM the time to peak filling rate was increased (p less than 0.05) and the filling fraction was decreased (p less than 0.01). In the patients with DCM cine MRI demonstrated normal volumes and ejection fraction of the right ventricle in contradistinction to the marked increase in volumes and the decrease in ejection fraction of the left ventricle; with the use of time-volume curves of the right ventricle, impairment of diastolic function of the right ventricle was demonstrated.

Adult↗

PubMed1991

Enhanced immunoreactivity of ras oncogene p21 protein in urinary bladder epithelium of rats treated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide.

Normal urothelium and various lesions of the rat urinary bladder induced by the dietary administration of 0.2% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) (up to 77 weeks) or by the combination of 0.2% FANFT and the subsequent administration of 5% sodium saccharin or 2% DL-tryptophan (up to 104 weeks) were evaluated for immunoreactivity with monoclonal antibody to ras p21 by avidin-biotin immunohistochemistry. Seventy-one to 100% of transitional cell carcinomas showed strong reactivity to the antibody to ras p21 depending on treatment with long-term administration of FANFT or by 6 weeks administration of FANFT followed by sodium saccharin or DL-tryptophan. Focal reactivity to the ras p21 antibody was frequently observed in the hyperplastic (57-96%) or normal appearing urinary bladder epithelium (50-100%) in rats treated with FANFT (FANFT alone or in combination with sodium saccharin or tryptophan) but not in hyperplasia or normal epithelium in rats given sodium saccharin or tryptophan alone, without pretreatment with FANFT or in untreated controls. The present results show that there is a close association of enhanced immunoreactivity with ras p21 antibody in the urinary bladder epithelium to FANFT treatment, and that ras p21 is expressed in normal, hyperplastic and neoplastic lesions of the bladder of rats treated with FANFT. These results suggest that enhanced immunoreactivity with ras p21 is observed as a consequence of the treatment with FANFT but it alone does not reflect the progression from benign to malignant lesions.

Animals↗

PubMed1991

Direct DNA sequencing of the rat neu oncogene transmembrane domain reveals no mutation in urinary bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl)nitrosamine, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide or N-methyl-N-nitrosourea.

Epidermal growth factor (EGF) and EGF-related growth factors are present in the urine, and EGF has been identified as a urinary component that enhances urinary bladder tumor formation in rats. Neu oncogene encodes a cell surface receptor similar to the EGF receptor and is known to be activated by a point mutation of DNA that encodes the transmembrane domain of the neu protein (p185). In this study, we examined the possible mutational activation of neu oncogene in 50 urinary bladder transitional cell carcinomas (TCC) induced in F344 rats by the following carcinogenesis models: (i) 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) (4 weeks)----3% uracil (20 weeks); (ii) 0.2% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) (6 weeks)----5% sodium saccharin (72 weeks); and (iii) N-methyl-N-nitrosourea (MNU) 20 mg/kg body wt, i.p. twice per week for 4 weeks----3% uracil (20 weeks). The DNA sequence around the transmembrane domain of neu gene was amplified by PCR and sequenced. 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.

Amino Acid Sequence↗

PubMed1991

Induction of invasive carcinomas of the seminal vesicles and coagulating glands of F344 rats by administration of N-methylnitrosourea or N-nitrosobis(2-oxopropyl)amine and followed by testosterone propionate with or without high-fat diet.

The potential modifying effects of testosterone propionate (TP) and high-caloric high-fat diet (20% corn oil, HF) on rat accessory sex gland carcinogenesis were investigated. Male F344 rats were treated five times at 4-week intervals with N-methylnitrosourea (MNU) i.v. or N-nitrosobis(2-oxopropyl)amine (BOP) s.c., each injection following 2 weeks pretreatment with dietary ethinyl estradiol. After completion of this carcinogen administration stage, animal groups received subcutaneous implantation of Silastic tubes filled with 40 mg TP with or without HF for 40 weeks. Carcinomas of the seminal vesicles and/or coagulating glands were induced in 5, 39 and 56% of rats given MNU alone, MNU and TP, and MNU and HF plus TP respectively. No equivalent tumors were found in rats given MNU and HF. In the BOP-treated groups, 11% of animals receiving TP but no HF diet demonstrated seminal vesicle carcinomas and 6% of rats receiving TP plus HF diet had coagulating gland carcinoma. Thus while TP exerted a strong enhancing effect on tumor growth in the seminal vesicles and coagulating glands, high caloric HF did not manifest any significant influence.

Animals↗

PubMed1991

In vitro transformation of rat bladder epithelium by 2-amino-4-(5-nitro-2-furyl)thiazole.

To establish a rat urinary bladder carcinogenesis model in vitro, primary rat bladder epithelial cells were grown in media containing 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT), the water-soluble metabolite of N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT), for 4 weeks followed by long-term (4-7 months) exposure to control medium, sodium saccharin (NaS), or urea. Another set of cultures were exposed to ANFT, NaS and urea simultaneously. Several phenotypic changes were observed in the chemically exposed cell cultures, namely differences in cell morphology, increased growth rate and the ability to grow on plastic instead of rat-tail collagen support. All of the chemically exposed cultures were anchorage independent except one of those treated with NaS. The ANFT-treated cells followed by control medium or urea and cells treated with ANFT, NaS and urea were tumorigenic when transplanted to nude mice, whereas NaS or ANFT followed by NaS treatment were not. The tumors were carcinomas and their epithelial differentiation was verified by strong positive staining for cytokeratin. These studies demonstrate the urothelial transforming capability of ANFT in cell culture without the necessity for a long exposure to a secondary chemical.

Animals↗