Rat urinary bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine and N-methyl-N-nitrosourea

Ozono, Seiichiro; K, Babaya; Sasaki, Kenji; Okamoto, Shingo; Momose, Hitoshi; Fujimoto, Kiyohide; Tsumatani, Kenichi; Yamaguchi, H.; Hirao, Yoshihiko; Okajima, Eijiro

doi:10.1007/bf00300780

Cited by 4 publications

(3 citation statements)

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“…Previous studies indicate that low doses of BBN induce tumors in the urothelium of rats and mice [Cohen 1998[Cohen , 2002, while MNU induces bladder cancer rapidly only after repeated instillation directly into the bladder [Hicks, 1980]. Some studies have been undertaken to evaluate the association between an additional treatment with MNU on the extent of invasion and H-ras and p53 mutations in TCC from rats bearing BBN-induced bladder neoplasias [Ozono et al, 1990;Shibata et al, 1994;Ozaki et al, 1997]. Although there were relatively few animals in the BBN-only group, our findings suggest that the MNU treatments promoted mouse bladder carcinogenesis since there was an increased frequency of invasive TCC in BBN/MNU-treated groups when compared with BBNonly.…”

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confidence: 99%

Effects of ginger (Zingiber officinale Roscoe) on DNA damage and development of urothelial tumors in a mouse bladder carcinogenesis model

Bidinotto

Spinardi-Barbisan

Rocha

et al. 2006

Environ and Mol Mutagen

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Extracts of the spice ginger (Zingiber officinale Roscoe) are rich in gingerols and shogaols, which exhibit antioxidant, anti-inflammatory, antifungal, antimycobacterial, and anticarcinogenic proprieties. The present study evaluated the chemoprotective effects of a ginger extract on the DNA damage and the development of bladder cancer induced by N-butyl-N-(4-hydroxibutyl) nitrosamine (BBN)/N-methyl-N-nitrosourea (MNU) in male Swiss mice. Groups G1-G3 were given 0.05% BBN in drinking water for 18 weeks and four i.p. injections of 30 mg/kg body weight MNU at 1, 3, 10, and 18 weeks. Group G4 and G5 received only the BBN or MNU treatments, respectively, and groups G6 and G7 were not treated with BBN or MNU. Additionally, Groups G2, G3, and G6 were fed diets containing 1, 2, and 2% ginger extract, respectively, while Groups G1, G4, G5, and G7 were fed basal diet. Samples of peripheral blood were collected during the experiment for genotoxicity analysis; blood collected 4 hr after each MNU dose was used for the analysis of DNA damage with the Comet assay (assay performed on leukocytes from all groups), while reticulocytes collected 24 hr after the last MNU treatment of Groups G5-G7 were used for the micronucleus assay. At the end of the experiment, the urinary bladder was removed, fixed, and prepared for histopathological, cell proliferation, and apoptosis evaluations. Ginger by itself was not genotoxic, and it did not alter the DNA damage levels induced by the BBN/MNU treatment during the course of the exposure. The incidence and multiplicity of simple and nodular hyperplasia and transitional cell carcinoma (TCC) were increased by the BBN/MNU treatment, but dietary ginger had no significant effect on these responses. However, in Group G2 (BBN/MNU/2% ginger-treated group), there was an increased incidence of Grade 2 TCC. The results suggest that ginger extract does not inhibit the development of BBN-induced mouse bladder tumors.

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confidence: 99%

Effects of ginger (Zingiber officinale Roscoe) on DNA damage and development of urothelial tumors in a mouse bladder carcinogenesis model

Bidinotto

Spinardi-Barbisan

Rocha

et al. 2006

Environ and Mol Mutagen

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“…However, significant tumor suppression was detected only in the BC31 xenograft model. In the BBN‐induced rat bladder cancer model, the incidence and size of tumors have been reported to be in accordance with concentration, duration and post–duration of BBN intake . The present study set a BBN intake for 10 weeks followed by 20 weeks of luteolin administration.…”

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confidence: 99%

Luteolin suppresses bladder cancer growth via regulation of mechanistic target of rapamycin pathway

et al. 2020

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Luteolin is a natural flavonoid with strong anti-oxidative properties that is reported to have an anti-cancer effect in several malignancies other than bladder cancer. In this study, we describe the effect of luteolin on a human bladder cancer cell line, T24, in the context of the regulation of p21, thioredoxin-1 (TRX1) and the mechanistic target of rapamycin (mTOR) pathway. Luteolin inhibited cell survival and induced G2/M cellcycle arrest, p21 upregulation and downregulation of phospho(p)-S6, which is downstream of mTOR signaling. Luteolin also upregulated TRX1 and reduced intracellular reactive oxygen species production. In a subcutaneous xenograft mouse model using the rat bladder cancer cell line, BC31, tumor volumes were significantly decreased in mice orally administered luteolin compared to control. Immunohistochemical analysis revealed that increased p21 and decreased p-S6 expression were induced in the luteolin treatment group. Moreover, in another in vivo N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced rat bladder cancer model, the oral administration of luteolin led to a trend of decreased bladder tumor dimension and significantly decreased the Ki67-labeling index and p-S6 expression. Furthermore, the major findings on the metabolism of luteolin suggest that both plasma and urine luteolin-3ʹ-O-glucuronide concentrations are strongly associated with the inhibition of cell proliferation and mTOR signaling. Moreover, a significant decrease in the squamous differentiation of bladder cancer is attributed to plasma luteolin-3ʹ-glucuronide concentration. In conclusion, luteolin, and in particular its metabolized product, may represent another natural product-derived therapeutic agent that acts against bladder cancer by upregulating p21 and inhibiting mTOR signaling. K E Y W O R D Sanimal model, bladder cancer, chemoprevention, mTOR, oxidative stress

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“…Druckrey et al [9] first described the carcinogenic effect of N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine (BBN) on the rat urinary bladder. Since then, this model system has been used by many investigators to study the histogenesis and the effects of various agents on the tumorigenesis and growth of bladder tumours [10–12]. In a preliminary experiment, we found that when 0.05% BBN was administered to rats daily for 8 weeks, bladder tumours developed in all rats and by the 20th week, 70–80% of these tumours were carcinomas.…”

Section: Introductionmentioning

confidence: 94%

Antitumour effects of the angiogenesis inhibitor AGM‐1470 on rat urinary bladder tumours induced by N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine

et al. 1999

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Rat urinary bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine and N-methyl-N-nitrosourea

Cited by 4 publications

References 4 publications

Effects of ginger (Zingiber officinale Roscoe) on DNA damage and development of urothelial tumors in a mouse bladder carcinogenesis model

Effects of ginger (Zingiber officinale Roscoe) on DNA damage and development of urothelial tumors in a mouse bladder carcinogenesis model

Luteolin suppresses bladder cancer growth via regulation of mechanistic target of rapamycin pathway

Antitumour effects of the angiogenesis inhibitor AGM‐1470 on rat urinary bladder tumours induced by N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine

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