SEARCH · PubMed Health

Results for “Butylhydroxybutylnitrosamine”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources

PubMed1990

Dose response of N-butyl-N-(4-hydroxybutyl)nitrosamine on urinary bladder carcinogenesis in mutant ODS rats lacking L-ascorbic acid synthesizing ability.

With a daily intake of 250 ppm total ascorbic acid, ODS and F344 male rats were given 0.0125%, 0.025% or 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in the drinking water for 12 weeks, and additional groups received 0.05% BBN for 2, 4 or 8 weeks. The experiment was terminated after a total of 36 weeks. A greater response to urinary bladder carcinogenesis was observed in both strains with increasing dose of BBN or longer treatment period. However, the magnitude of urinary bladder carcinogenesis in ODS rats given the higher BBN concentrations and/or long periods of BBN treatment was less than in comparably treated F344 rats, but not with lower concentrations of BBN and/or shorter periods of BBN treatment.

Animals↗

PubMed1990

Involvement of urine in epithelial-stromal interactions in urinary bladder carcinogenesis.

The role of urine in epithelial-stromal interactions in urinary bladder carcinogenesis was investigated using the 'Stroma' bladder model established in our laboratory. Rats treated with 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BHBN) in drinking water for 4 weeks or age-matched untreated rats served as donors of bladders with denuded epithelium ('stroma' bladders), which were resurfaced 4 days later with urothelial cells from rats treated with 0.05% BHBN for 4 weeks. Subsequently, the transplants received weekly injections of normal rat urine or saline. In the urine-free environment, cell implants developed hyperplastic changes but few tumor formations with no significant difference between the two types of 'stroma' bladder. In contrast, urine instillation stimulated neoplastic growth, and tumor-enhancing effect was significantly accelerated in the BHBN-treated 'stroma' bladder group as compared to the control group. These results suggest that epithelial-stromal interactions are altered in such a way that bladder carcinogenesis is enhanced by prior exposure of the bladder stroma to carcinogen and subsequent urine contact.

Animals↗

PubMed1991

Lack of synergism in rat urinary tract carcinogenesis between prior uracil treatment and N-butyl-N-(4-hydroxybutyl)-nitrosamine administration.

Combination effects of sequential treatment with uracil prior to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) with regard to carcinogenesis in the urinary bladder and renal pelvis were investigated in male F344 rats. Uracil was administered for 15, 10 or 5 weeks followed by BBN for 23 weeks, the total observation time being 40 weeks. Carcinoma(s) and papilloma(s) were induced in the urinary tract by the 15-week uracil treatment independent of subsequent BBN administration. It was concluded that uracil administration prior to BBN treatment is not associated with any synergistic effects, although both uracil and BBN alone exerted carcinogenicity.

Animals↗

PubMed1994

Influences of aging and sex on renal pelvic carcinogenesis by N-butyl-N-(4-hydroxybutyl)nitrosamine in NON/Shi mice.

Influences of aging and sex on renal pelvic carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were examined in 6-, 15 -and 45-week-old male and female NON/Shi mice. Histopathological examination revealed an age-related shortening of induction time for renal pelvic carcinomas in males, although actual incidences did not increase. The histological patterns of carcinomas induced in both renal pelvis and urinary bladder demonstrated male mice to be more prone to develop transitional cell carcinomas, while squamous cell carcinomas were more likely to arise in females. Moreover, the sex factor appeared to influence the progression of both renal pelvic and urinary bladder carcinomas.

Aging↗

PubMed1995

Modulating effects of ellagic acid, vanillin and quercetin in a rat medium term multi-organ carcinogenesis model.

Effects of dietary supplementation with the antioxidants ellagic acid, quercetin and vanillin were examined using a medium term multi-organ carcinogenesis model in rats. Groups of 10-15 male F344 rats were given i.p. injections of diethylnitrosamine (DEN, 100 mg/kg body wt.) and N-methylnitrosourea (MNU, 20 mg/kg body wt), s.c. injections of 1,2-dimethylhydrazine (DMH, 40 mg/kg body wt.), together with 0.05% N-butyl-N-(4- hydroxybutyl)nitrosamine (BBN) and 0.1% 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN), both in the drinking water, for a total multiple initiation period of 4 weeks (DMBDD) treatment). Ellagic acid, quercetin or vanillin, each at a dose of 1% each in the diet were administered from 1 day before and throughout the carcinogen exposure period, or after completion of the initiation regimen. All surviving animals were sacrificed at the end of week 36, and major organs were examined histopathologically. In the small intestine, significant reductions in the incidence and number of tumors (adenomas and carcinomas) were observed in the groups administered ellagic acid during (8%, 0.08 +/- 0.29) or after (8%, 0.08 +/- 0.29) DMBDD treatment, and those receiving quercetin after DMBDD treatment (0%) compared to the control value (57%, 1.07 +/- 1.21). Although the incidences were not statistically significant, slightly decreased numbers of small intestinal tumors were found in the groups receiving vanillin during (0.33 +/- 0.72), or after (0.40 +/- 0.83) DMBDD treatment. The incidence of large intestinal carcinomas in the group treated with vanillin during DMBDD treatment was significantly higher (73%) than the control value (21%). These results indicated that while ellagic acid and quercetin exerted potent chemopreventive action in both the initiation and promotion stages in the present experimental system, their beneficial effects were restricted to the small intestine. Since small intestinal carcinomas are very infrequent in humans, the advantages of these phenolic compounds for human application as chemopreventors should not be overestimated.

1,2-Dimethylhydrazine↗

PubMed1996

p53 mutations in transitional cell carcinomas of the urinary bladder in rats treated with N-butyl-N-(4-hydroxybutyl)-nitrosamine.

Involvement of p53 gene alterations has been demonstrated in a variety of human neoplasias including urinary bladder carcinomas. N-Butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced urinary bladder carcinogenesis models in rodents have been widely used to study carcinogenic processes in this organ. In the present study, transitional cell carcinomas induced in the urinary bladders of male F344 rats treated with 0.05% BBN for 16 or 32 weeks and then sacrificed at experimental week 32 were analyzed for mutational changes in the p53 and H-ras genes by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and subsequent DNA sequencing. The total p53 mutation incidences were 3/10 (30%) and 8/12 (66.7%) in rats treated with BBN for 16 weeks followed by 16 weeks' non-treatment, or in rats treated with BBN for 32 weeks, respectively, while the H-ras mutation incidences were 0/10 (0%), and 1/12 (8.3%), respectively. The present results indicate that mutations in the p53 gene might be involved in the process of urinary bladder carcinogenesis by BBN as part of a multistep pathway. However, considering the decreasing tendency in lesions with p53 mutations after stopping BBN administration, a p53 mutation alone would not appear to be sufficient to give a marked selective advantage to mutant cells. No evidence of H-ras mutation involvement was gained even for the late course of rat urinary bladder carcinogenesis.

Animals↗

PubMed1988

Effects of urinary crystals induced by acetazolamide, uracil, and diethylene glycol on urinary bladder carcinogenesis in N-butyl-N-(4-hydroxybutyl)nitrosamine-initiated rats.

In order to examine the promoting effect of urinary crystals on urinary bladder carcinogenesis, acetazolamide, uracil, and diethylene glycol, all of which have been reported to cause urinary crystals or calculi, were administered to male F344 rats for 32 weeks after pretreatment with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 weeks. A marked increase in urinary crystals was observed in acetazolamide-treated rats and a slight increase in crystals was observed in uracil- and diethylene glycol-treated rats. Histological examination of the urinary bladder revealed that the BBN-acetazolamide treatment resulted in a higher incidence of carcinoma than BBN-control. Uracil and diethylene glycol did not cause any significant difference compared to the control. Promoting effects by urinary crystals were not clearly shown in the present experiment and, therefore, urinary crystals appear to play a very limited role, if any, in urinary bladder carcinogenesis.

Acetazolamide↗

PubMed2006

Chemically induced bladder cancer--a sonographic and morphologic description.

OBJECTIVES: Carcinogen-induced bladder cancer in rodents is a key model for evaluation of novel therapies for bladder cancer because of its similarity to the clinical disease. The major drawback of the model is the difficulty in assessing tumor burden in living animals and at necropsy. The objective of this work was to present simple and accurate solutions for this problem. METHODS: Sixty female Wistar rats were given N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) at a concentration of 0.05% in the drinking water for 35 weeks. Periodic evaluation of tumorigenesis was done by ultrasonography of the anesthetized animals. The tumor burden was evaluated after killing the rats by weighing the bladder, digital measurement of the tumor dimensions, and histologic examination. RESULTS: Focal urothelial hyperplasia was noted by the 5th BBN week, severe dysplasia by the 15th BBN week, and transitional cell carcinoma from the 20th week on. Carcinoma was seen on digital photographs taken from the 20th week on. Tumors as small as 1 mm could be easily measured. A poor correlation (R2 = 0.33) was found between bladder weight and the digital photographic measurements of small tumors (20th BBN week). However, when larger tumors were considered (30th BBN week), a good correlation was found (R2 = 0.81). CONCLUSIONS: Tumor progress in the rat BBN model was accurately monitored by ultrasonography in living animals. Digital measurement of tumor dimensions provided a precise method for evaluation of tumor burden at necropsy.

Animals↗

PubMedDate not supplied

Induction of repair synthesis of DNA in primary cultures of rat urothelial cells by derivatives of the bladder carcinogen, N-n-butyl-N-(4-hydroxybutyl)nitrosamine.

Urinary metabolites of N-n-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN) which have been identified thus far did not induce repair synthesis of DNA in cultured rat urothelial cells. Urine of rats which had been administered with BHBN or BCPN did not induce repair synthesis of DNA either. However, all the synthetic nitrosamines that can produce 1-hydroxyalkylnitrosamine intermediates induced repair synthesis of DNA. The results suggest that rat urothelial cells, at best, may only have very limited capability of activating nitrosamines.

Animals↗

PubMed1991

Enhancing effect of partial cystectomy on rat urinary bladder carcinogenesis.

The effects of 5% and 50% partial cystectomies on bladder tumorigenesis initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine(BBN) were investigated in Wistar rats by examining the histological findings and cell proliferative activity. The incorporation of bromodeoxyuridine (BrdUrd) into the DNA synthesis phase was determined by an in-vitro labeling technique. After eight weeks of treatment with drinking water containing 0.05% BBN, 5% or 50% partial cystectomy was performed at the end of week 16, and the resected bladder was sutured with dexon or silk. There was no difference in the incidence of papillary or nodular (PN) hyperplasia between the control and partial cystectomy groups. However, the incidence of cancer in the group given partial cystectomy was much higher than that in the control. All the cancers in the control group were grade-1 superficial tumors, whereas grade-2 or invasive tumor was observed in six of 40 animals in the partial cystectomy group. The 31.0% labeling index of cancer in the partial cystectomy group was greater than the 24.1% in the control group. There was also a significant difference in the number of BrdUrd-labeled cells in PN hyperplasia between the control and partial cystectomy groups. These findings indicate that partial cystectomy enhances BBN-initiated bladder carcinogenesis and the increase in DNA synthesis found in PN hyperplasia and cancer may be associated with the induction of bladder tumors.

Animals↗

PubMed1990

The kinetics of cellular proliferation in rat urinary bladder treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

The cellular proliferation of the bladder epithelium was determined sequentially in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). The incorporation of bromodeoxyuridine (BrdUrd) into the DNA synthesis phase was determined by an in vitro labeling technique. The percentage of labeled cells was expressed as the labeling index (LI). The average LI values in normal subjects and cancer-bearing subjects were 5.1(%) and 24.2(%) respectively. With the transition of the bladder epithelium from simple hyperplasia to cancer, the LI values of the bladder epithelium were increased. Cases of papillary or nodular (PN) hyperplasia were divided into two types according to the localization of the BrdUrd-labeled cells. The LI in PN hyperplasia was 12.4(%); the difference from cancer was significant. In another experiment, the effect of partial cystectomy on bladder tumors was examined. The group with partial cystectomy showed increases in grade and stage of cancer, and the LI of cancer was more than that in the group without partial cystectomy. The results indicate that partial cystectomy may play a role as promotor for bladder tumors. The current study may be of more practical value than is the conventional one for investigating the histogenesis and progression of human bladder cancer.

Animals↗

PubMed1990

Stimulation of urinary bladder tumorigenesis by carcinogen-exposed stroma.

There is evidence to suggest that control mechanisms, either growth-stimulatory, inhibitory or inductive, may play a role in carcinogenesis. To test the hypothesis that treatment of rat urinary bladder with carcinogen induces alterations in the stroma which result in modified epithelial-stromal interactions, experiments were conducted using a rat model specifically designed for the study. Following exposure of Fischer F344 rats in drinking water to the urinary bladder carcinogen, N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN) for four weeks, bladders were removed and subjected to a brief detergent treatment to completely remove epithelium. The bladders without epithelium ("stroma" bladder) were heterotopically transplanted to syngeneic recipients. Four days later, the denuded mucosa surface was resurfaced with intraluminal instillation of urothelial cells, either untreated or treated with BHBN for six weeks (6w-BHBN) or 10 weeks (10w-BHBN). Examination at 12 weeks posttransplant of the "stroma" bladders that had received 6w-BHBN urothelial cells showed a higher tumor incidence of carcinoma in the BHBN-exposed "stroma" bladders as compared with the incidence in the carcinogen-unexposed "stroma" bladders (p less than 0.05). Examination at 18 weeks posttransplant showed 100% incidence of tumors in all "stroma" bladders irrespective of the lengths of BHBN exposure of urothelial cells. However, among the bladders that had received 6w-BHBN urothelial cells, carcinogen-exposed "stroma" bladders proved to be better "soil" for neoplastic cells to proliferate; the mean tumor volume as well as the mean total tumor volume per bladder were significantly higher than in the control "stroma" bladders (p less than 0.01 for each comparison). Similarly, among the bladders that had been resurfaced with 10w-BHBN urothelial cells, the mean total tumor volume per bladder was greater in the carcinogen-treated "stroma" bladders than in the controls (p less than 0.05). No proliferative or neoplastic changes were observed in the BHBN exposed "stroma" bladders which had been resurfaced with normal urothelial cells. Our data indicate that neoplastic growth of carcinogen treated urothelium is enhanced when such cells interact with the stroma which has also been exposed to carcinogen.

Animals↗

PubMed1989

Suppression of rat urinary bladder carcinogenesis by alpha-difluoromethylornithine.

The inhibitory effect of oral administration of alpha-difluoromethylornithine (DFMO) on urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BHBN) was explored. Since DFMO in the drinking water at 0.5% and 0.2% had been demonstrated to inhibit tumorigenesis, lower doses (0.2%, 0.1%, 0.03% and 0.01%) of DFMO were examined in the present study. After six-week treatment with the drinking water containing 0.05% BHBN, water containing DFMO at 0.2%, 0.1%, 0.03%, 0.01% or 0% was administered during the subsequent 34 weeks. Incidence of bladder carcinoma was 15/35 (43%), 14/35 (40%), 21/35 (60%), 20/35 (57%) and 27/35 (77%) in the 0.2%, 0.1%, 0.03%, 0.01% and 0% DFMO groups, respectively. Stastistical analysis indicated significant tumor suppression in the 0.2% and 0.1% DFMO groups. Tumor multiplicity and size were not affected by DFMO treatment. No untoward effects were demonstrated in body weight gain or examination of pertinent organs. Our data indicate that bladder carcinogenesis induced by six-week exposure to 0.05% BHBN is significantly inhibited by daily administration of DFMO at the level of 0.1% or higher in drinking water.

Administration, Oral↗

PubMed1988

Effect of continuous intravesical infusion of low-concentrated mitomycin-C on bladder carcinogenesis in rats treated with N-butyl-N-4-hydroxybutyl-nitrosamine.

In the first experiment, histological changes of urinary bladder after long-term transvesical catheterization were evaluated in normal rats. No malignant changes of the bladder epithelium were detected in the two and four-week catheterization groups. However incidences of papilloma and papillary carcinoma developed in three of the five rats (60%) in the eight-week group. In a second experiment the therapeutic effect of continuous or intermittent administration of MMC on bladder carcinogenesis in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined. MMC at a total dose of four mg. was administered for two weeks in both therapeutic groups. Continuous infusion was performed transvesically using an osmotic pump and a silicone catheter, on the basis that preliminary examination revealed the urinary delivery rate of MMC was constant for two weeks. In the intermittent group, MMC solution was instilled transurethrally with a venural catheter twice a week. The continuous infusion of low concentrated MMC reduced significantly (p less than 0.02) the incidence of tumor development in spite of extended catheterization (for eight weeks) into the bladder. However, the intermittent instillation of high concentrated MMC hardly inhibited the development of bladder tumors. We should consider the optimal concentration and time of a drug in intravesical chemotherapy based on the above findings.

Administration, Intravesical↗

PubMed1987

Effects of intravesical instillation of antitumor chemotherapeutic and immunotherapeutic agents on bladder lesion development in rats pretreated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

The effects of 12 weeks of intravesical instillation of bleomycin, cisplatinum and picibanyl on development of urinary bladder tumors and preneoplastic lesions were examined in rats pretreated with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) for four weeks. Upon sacrifice at week 36, histopathological examination revealed a significantly reduced incidence of PN hyperplasia and a tendency for decreased papilloma generation in rats given cisplatinum. However, the other treatments were not associated with any effect on carcinogen-induced lesion development. The results demonstrate that cisplatinum has a potential for postinitiation inhibition of rat bladder carcinogenesis.

Administration, Intravesical↗

PubMed1987

Analyses of avidin-biotin complexes with lectins of membrane glycoproteins in the urinary bladder of rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

The bladder epithelium was examined by staining with avidin-biotin complexes with lectins to determine the early membrane changes during bladder carcinogenesis in rats treated with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BHBN). Concanavalia ensiformis (Con A), Triticum vulgaris (WGA), Ricinus communis (RCA) and Arachis hypogaea (PNA) were used as probes. The cellular distributions of lectin particles were distinguished into membranous and cytoplasmic patterns. Normal bladder cells stained very slightly and showed a spotty membranous pattern. After treatment of rats with BHBN for two or three weeks, staining became stronger and its pattern changed from a membranous to a cytoplasmic type. The staining of bladder cancer cells induced by BHBN varied from area to area and with different lectins. These data indicated that changes in carbohydrates occur in the bladder cell membrane during the early phase of carcinogenesis.

Animals↗

PubMed1982

Cytochemical studies of LDH isoenzymes in experimental bladder tumors.

Cytomorphologic or histologic changes in the tumorigenic process of the urinary bladder epithelium and the corresponding cytochemical alteration of lactate dehydrogenase (LDH) isoenzymes were studied in rats given a bladder carcinogen, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). All the rats given BBN as drinking water for about 8 weeks showed hyperplasia of the bladder epithelium and all the rats given BBN for about 16 weeks developed papillomas. Carcinomas were noticed in 81 per cent of the animals given the carcinogen for 20 weeks. Urinary cytology showed no malignant cells before the 12th week but detected exfoliated malignant cells in 14 per cent of the rats given the carcinogen for 16 weeks. Malignant cells were found in 57 and 95 per cent of animals sacrificed at the 20th and 24th week respectively. Alteration of LDH isoenzyme pattern of cell extracts from the bladder epithelium that is characterized by shift to LDH4 and LDH5 from the preponderance of LDH1 and LDH2 in normal epithelium preceded the morphologic change; it appeared as early as the 8th week. A reversion of M/H ratio of the isoenzyme pattern could be proved cytochemically by means of urea inhibition that inactivates the LDH M-subunit.

Animals↗

PubMed2001

Possible involvement of O6-methylguanine formation and p53 dysfunction in mouse urinary bladder carcinogenesis.

The significance of O6-methylguanine formation in urinary bladder carcinogenesis was examined using O6-methylguanine-DNA methyltransferase (MGMT) transgenic mice carrying the ada gene. The ada MGMT transgenic mice demonstrated no differences in development of carcinogens-induced urinary bladder carcinomas compared with non-transgenic mice. Furthermore, no variation in p53 mutation frequency was evident between the two groups. The results indicated that other repair systems may have an important role for urinary bladder carcinogenesis. p53 knockout mice showed high sensitivity to urinary bladder carcinogens and increased cell proliferation plays an important role in urinary bladder carcinogenicity of p53 knockout mice. In addition, p53 knockout mice have an organ-specific increased sensitivity to carcinogenicity.

Animals↗