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Japanese Journal of Cancer Research :... Jan 2000We studied the susceptibilities to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced urinary bladder carcinogenesis of male Long-Evans Cinnamon (LEC), F344 and...
We studied the susceptibilities to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced urinary bladder carcinogenesis of male Long-Evans Cinnamon (LEC), F344 and Long-Evans Agouti (LEA) rats. Male rats (n=21) were given 0.1% BBN in their drinking water from week 6, 8 and 10 for one week, and killed in week 56. The incidences of transitional cell tumors (papillomas plus carcinomas) in BBN-treated LEC and F344 rats were 12% and 76%, respectively (P<0.001, experiment 1), and those in LEC and LEA rats were 11% and 95%, respectively (P<0.001, experiment 2). When male LEC and F344 rats were given 0.1% BBN in their drinking water for 7 days, the intake of BBN and the urinary concentration of its active metabolite, N-butyl-N-(3-carboxypropyl)nitrosamine (BCPN), were higher in the LEC rats (P<0.01). The urinary pHs of untreated LEC and F344 rats were similar between week 6 and 30. The urinary copper concentration was lower in LEC rats before jaundice than in F344 rats, but its concentrations in 28- and 50-week-old LEC rats were 1.7 and 2.3 times those in F344 rats. In a two-stage carcinogenesis study using F344 rats, i.p. injections of cupric nitrilotriacetate increased urinary copper excretion, and inhibited BBN-induced bladder carcinogenesis. In a two-stage carcinogenesis study using LEC rats, oral administration of D-penicillamine decreased urinary copper excretion, and increased BBN-induced bladder cancer, although the difference was not significant. These data show that LEC rats are resistant to bladder carcinogenesis and suggest that urinary copper has a significant role in their resistance.
Topics: Age Factors; Animals; Butylhydroxybutylnitrosamine; Carcinogens; Chelating Agents; Copper; Copper Sulfate; Disease Susceptibility; Hydrogen-Ion Concentration; Iron; Male; Metallothionein; Penicillamine; Rats; Rats, Inbred F344; Rats, Inbred LEC; Rats, Long-Evans; Species Specificity; Urinary Bladder Neoplasms; Urine; Zinc
PubMed: 10744040
DOI: 10.1111/j.1349-7006.2000.tb00855.x -
British Journal of Cancer May 1977Pulse doses of N-dibutylnitrosamine(DBN), N-butyl-N-(4-hydroxybutyl)nitrosamine(BBN) and N-butyl-N-(3carboxypropyl)nitrosamine(BCPN) suspended in 1% gelatin, were... (Comparative Study)
Comparative Study
Pulse doses of N-dibutylnitrosamine(DBN), N-butyl-N-(4-hydroxybutyl)nitrosamine(BBN) and N-butyl-N-(3carboxypropyl)nitrosamine(BCPN) suspended in 1% gelatin, were administered s.c. to infant CDF1 mice, and the experiment terminated at one year of age. Tumours were induced in lungs and liver. The incidences of lung adenomas were 73-95% in all treated mice, with no sex differences. Hepatocellular adenomas and a carcinoma were found with an incidence of 81% (21/26) in DBN, 59% (13/22) in BBN, and 32% (9/28) in BCPN-treated males and the incidence was 23% (5/22) in DBN-treated females. Only one papilloma of the fore-stomach was induced in mice treated with DBN. These results indicated that the s.c. administration of DBN, BBN, and BCPN induced tumours of the lung and liver, but no tumours of the urinary bladder, under these experimental conditions. The carcinogenic effect on mice at the treated dose level was DBN greater than BBN greater than BCPN.
Topics: Adenoma; Animals; Butylhydroxybutylnitrosamine; Carcinoma; Female; Liver Neoplasms; Lung Neoplasms; Male; Mice; Mice, Inbred Strains; Neoplasms, Experimental; Nitrosamines; Time Factors
PubMed: 861148
DOI: 10.1038/bjc.1977.95 -
Journal of the Royal Society of Medicine Jan 1983
Review
Topics: Animals; Bacterial Infections; Butylhydroxybutylnitrosamine; Child; Egypt; Female; Humans; Male; Nitrosamines; Papio; Schistosoma haematobium; Schistosomiasis; Sex Factors; Urinary Bladder Neoplasms; Urinary Tract Infections
PubMed: 6338226
DOI: 10.1177/014107688307600105 -
Japanese Journal of Cancer Research :... Jun 1991A sequential investigation of N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) bladder carcinogenesis was performed in male B6C3F1 mice maintained ad libitum on tap water...
A sequential investigation of N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) bladder carcinogenesis was performed in male B6C3F1 mice maintained ad libitum on tap water containing 0.025% EHBN for 4, 12, 20, 28 and 36 weeks. A total of 81 invasive tumors, comprising 55 squamous cell carcinomas (SCCs) (68%), 25 transitional cell carcinomas (TCCs) (31%) and 1 adenocarcinoma (1%) were found. Of these, 23 (22 SCCs and 1 TCC) demonstrated invasion to the prostate, 3 metastasized to the lung, and 2 spread by peritoneal seeding. The anaplastic grade and extent of invasion of the SCCs significantly exceeded those of the TCCs. The results suggested a histogenetic pathway from simple dysplasia through papillary or nodular dysplasia and/or carcinoma in situ to eventual development of invasive carcinomas.
Topics: Animals; Butylhydroxybutylnitrosamine; Carcinogens; Carcinoma in Situ; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Dose-Response Relationship, Drug; Epithelium; Male; Mice; Mice, Inbred Strains; Neoplasm Invasiveness; Time Factors; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 1906851
DOI: 10.1111/j.1349-7006.1991.tb01900.x -
Hinyokika Kiyo. Acta Urologica Japonica Nov 1988Treatment with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) or N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) in the drinking water induces bladder cancer of rats or mice... (Comparative Study)
Comparative Study
Treatment with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) or N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) in the drinking water induces bladder cancer of rats or mice with high incidence. Induced bladder cancers of rats are mostly papillary, non-invasive type, whereas those of mice are non-papillary, invasive type. Histologically, most of BBN-induced bladder cancers are transitional cell carcinoma in both rats and mice. On the other hand, the incidences of squamous cell carcinoma increased in cases of mice, especially in mice treated with EHBN. Metastases and invasions of bladder cancers are more common in mice than in rats. There are strain and species differences in the bladder response to BBN and EHBN. In addition, a putative preneoplastic lesion, papillary or nodular hyperplasia of the epithelium is a good marker for early detection of bladder cancer development.
Topics: Animals; Butylhydroxybutylnitrosamine; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Chemical Phenomena; Chemistry; Disease Models, Animal; Mice; Neoplasm Invasiveness; Neoplasm Metastasis; Precancerous Conditions; Rats; Urinary Bladder Neoplasms
PubMed: 3242366
DOI: No ID Found -
International Journal of Experimental... Feb 2007To examine DNA abnormalities in bladder papillary tumours induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in female rats, using image cytometric DNA analysis and...
To examine DNA abnormalities in bladder papillary tumours induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in female rats, using image cytometric DNA analysis and cytogenetics. Thirty female rats were exposed to BBN in their drinking water for 20 weeks. One group of 10 animals served as controls. The animals exposed to BBN were killed at a rate of two per week, with the bladder being collected under aseptic conditions and those tumours with exophytic growth removed. The nuclear DNA content of the tumours was evaluated using image cytometric analysis. In two rats part of the tumour pieces was stipulated for culturing. Cytogenetic analysis was performed on at least 30 cells from each cell population and on both tumours. Papillary carcinomas were classified as low grade and high grade. DNA ploidy studies were carried out on 28 low-grade and 21 high-grade papillary carcinomas. Histograms obtained by image analysis showed that a normal urothelium was diploid; 28.6% and 100% of low-and high-grade papillary carcinomas were aneuploid respectively. Both tumours used for cell culture showed multiple numerical and structural chromosome alterations and several marker chromosomes. Image cytometric DNA analysis proved to be a good and reliable method for examining DNA alterations in papillary bladder carcinomas. The present findings establish that the DNA content is statistically different between low-grade and high-grade papillary carcinomas and that deviation from the diploid number is markedly higher in the high-grade ones. In addition, the occurrence of marker chromosomes seems to be related to the aggressiveness of the tumour.
Topics: Animals; Butylhydroxybutylnitrosamine; Carcinogens; Carcinoma, Papillary; Chromosome Aberrations; Cytogenetics; DNA, Neoplasm; Female; Neoplasms, Experimental; Rats; Rats, Inbred F344; Urinary Bladder Neoplasms; Urothelium
PubMed: 17244337
DOI: 10.1111/j.1365-2613.2006.00517.x -
Hinyokika Kiyo. Acta Urologica Japonica Jun 2006In this paper, we report on invasive urinary bladder carcinomas as follows, (1) p53 mutations have an important role in promotion and progression stages of...
In this paper, we report on invasive urinary bladder carcinomas as follows, (1) p53 mutations have an important role in promotion and progression stages of carcinogenesis, (2) invasive bladder carcinomas occur multi-centrically in the bladder, (3) an organic arsenic, dimethylarsinic acid exerts carcinogenicity in the bladder of rats, (4) p53 mutations in carcinomas are caused by different carcinogens, and (5) bladder urothelium of people living in 137Cs-contaminated areas of Ukraine showed chronic proliferative atypical cystitis (so-called Chernobyl cystitis).
Topics: Animals; Butylhydroxybutylnitrosamine; Carcinoma, Transitional Cell; Chernobyl Nuclear Accident; Female; Male; Mice; Mice, Knockout; Mutation; Neoplasms, Radiation-Induced; Rats; Tumor Suppressor Protein p53; Ukraine; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 16848359
DOI: No ID Found -
Journal of Controlled Release :... Feb 2014The Mycobacterium bovis Bacille Calmette-Guerin cell wall skeleton (BCG-CWS) could be used to replace live BCG as a bladder cancer drug. However, because BCG-CWS is...
The Mycobacterium bovis Bacille Calmette-Guerin cell wall skeleton (BCG-CWS) could be used to replace live BCG as a bladder cancer drug. However, because BCG-CWS is poorly soluble, has a strong-negative charge, very high molecular weight and heterogeneity in size of tens of μm, it cannot be used in such an application. We report herein on the development of a novel packaging method that permits BCG-CWS to be encapsulated into 166nm-sized lipid particles. The BCG-CWS encapsulated nano particle (CWS-NP) has a high uniformity and can be easily dispersed. Thus, it has the potential for use as a packaging method that would advance the scope of applications of BCG-CWS as a bladder cancer drug. In a functional evaluation, CWS-NP was efficiently taken up by mouse bladder tumor (MBT-2) cells in vitro and inhibited tumor growth in mice bearing MBT-2 tumors. Moreover, intravesically administered CWS-NP showed significant antitumor effects in a rat model with naturally developed bladder cancer. An enhancement in Th1 differentiation by CWS-NP was also confirmed in human T cells. In conclusion, CWS-NP represents a promising delivery system for BCG-CWS for clinical development as a potent bladder cancer drug.
Topics: Adult; Animals; Antineoplastic Agents; Butylhydroxybutylnitrosamine; Cell Differentiation; Cell Line, Tumor; Cell Wall Skeleton; Cells, Cultured; Female; Humans; Male; Mice; Mice, Inbred C3H; Mycobacterium bovis; Nanoparticles; Rats; Rats, Inbred F344; T-Lymphocytes; Urinary Bladder Neoplasms; Young Adult
PubMed: 24389133
DOI: 10.1016/j.jconrel.2013.12.027 -
Journal of Visualized Experiments : JoVE Oct 2013A preclinical model of invasive bladder cancer was developed in human mucin 1 (MUC1) transgenic (MUC1.Tg) mice for the purpose of evaluating immunotherapy and/or...
A preclinical model of invasive bladder cancer was developed in human mucin 1 (MUC1) transgenic (MUC1.Tg) mice for the purpose of evaluating immunotherapy and/or cytotoxic chemotherapy. To induce bladder cancer, C57BL/6 mice (MUC1.Tg and wild type) were treated orally with the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN) at 3.0 mg/day, 5 days/week for 12 weeks. To assess the effects of OH-BBN on serum cytokine profile during tumor development, whole blood was collected via submandibular bleeds prior to treatment and every four weeks. In addition, a MUC1-targeted peptide vaccine and placebo were administered to groups of mice weekly for eight weeks. Multiplex fluorometric microbead immunoanalyses of serum cytokines during tumor development and following vaccination were performed. At termination, interferon gamma (IFN-γ)/interleukin-4 (IL-4) ELISpot analysis for MUC1 specific T-cell immune response and histopathological evaluations of tumor type and grade were performed. The results showed that: (1) the incidence of bladder cancer in both MUC1.Tg and wild type mice was 67%; (2) transitional cell carcinomas (TCC) developed at a 2:1 ratio compared to squamous cell carcinomas (SCC); (3) inflammatory cytokines increased with time during tumor development; and (4) administration of the peptide vaccine induces a Th1-polarized serum cytokine profile and a MUC1 specific T-cell response. All tumors in MUC1.Tg mice were positive for MUC1 expression, and half of all tumors in MUC1.Tg and wild type mice were invasive. In conclusion, using a team approach through the coordination of the efforts of pharmacologists, immunologists, pathologists and molecular biologists, we have developed an immune intact transgenic mouse model of bladder cancer that expresses hMUC1.
Topics: Animals; Butylhydroxybutylnitrosamine; Cancer Vaccines; Carcinogens; Carcinoma, Transitional Cell; Cytokines; Disease Models, Animal; Female; Humans; Immunotherapy; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mucin-1; T-Lymphocytes, Cytotoxic; Urinary Bladder Neoplasms
PubMed: 24300078
DOI: 10.3791/50868 -
Japanese Journal of Cancer Research :... Jun 2000Chemopreventive effects of bovine lactoferrin (bLF), which is found at high concentrations in colostrum, on rat bladder carcinogenesis were investigated using a rat...
Chemopreventive effects of bovine lactoferrin (bLF), which is found at high concentrations in colostrum, on rat bladder carcinogenesis were investigated using a rat bladder medium-term bioassay. In experiment 1, a total of 80 F344 male rats, 6 weeks old, were divided into 5 groups. Groups 1 and 2 were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in the drinking water for 8 weeks and after a 1-week interval, received dietary supplementation with 2% and 0.2% bLF, respectively. Group 3 received 0.05% BBN for 8 weeks and then no treatment. Group 4 was administered 2% bLF alone from week 9, without prior carcinogen exposure. Group 5 was maintained without any treatment throughout the experiment. All rats were killed at the end of week 36. Group 1 demonstrated a significantly decreased multiplicity of the bladder tumors (carcinomas and papillomas) as compared with group 3. Maximum cut surface areas of bladder tumors were also significantly decreased in groups 1 and 2 compared with group 3. No bladder tumors were observed in groups 4 or 5. In experiment 2, a total of 60 rats were divided into two groups (30 rats each); both were treated with 0.05% BBN for 4 weeks and after a 1-week interval, one received 2% bLF (group 1) and the other, basal diet (group 2) for 4 weeks. Group 1 demonstrated a tendency for decrease of the 5-bromo-2'-deoxyuridine (BrdU) labeling index. bLF was detected in the urine of rats fed bLF by ELISA as well as western blot analysis. The findings indicate that 2% bLF can inhibit BBN-induced rat bladder carcinogenesis, and that this may be due to bLF in the urine.
Topics: Acetyltransferases; Animals; Anticarcinogenic Agents; Body Weight; Butylhydroxybutylnitrosamine; Carcinogens; Cattle; Chlorides; Drinking; Eating; Hydrogen-Ion Concentration; Lactoferrin; Liver; Male; Mucous Membrane; Organ Size; Ornithine Decarboxylase; Potassium; Rats; Rats, Inbred F344; Sodium; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 10874209
DOI: 10.1111/j.1349-7006.2000.tb00985.x