Absence of DNA damage in multiple organs (blood, liver, kidney, thyroid gland and urinary bladder) after acute fluoride exposure in rats

Fluoride has been widely used in dentistry as a caries prophylactic agent. However, there has been some speculation that excess fluoride could cause an impact on genome integrity. In the current study, the potential DNA damage associated with exposure to fluoride was assessed in cells of blood, liver, kidney, thyroid gland and urinary bladder by the single cell gel (comet) assay. Male Wistar rats aging 75 days were distributed into seven groups: Groups 1 (control), 2, 3, 4, 5, 6 and 7 received 0 (deionized water), 10, 20, 40, 60, 80 and 100 mgF/Kg body weight from sodium fluoride (NaF), respectively, by gastrogavage. These groups were killed at 2 h after the administration of the fluoride doses. The level of DNA strand breaks did not increase in all organs evaluated and at all doses of NaF tested, as depicted by the mean tail moment. Taken together, our results suggest that oral exposure to NaF did not result in systemic genotoxic effect in multiple organs related to fluoride toxicity. Since DNA damage is an important step in events leading to carcinogenesis, this study represents a relevant contribution to the correct evaluation of the potential health risk associated with chemical exposure.

Diuron-Induced Rat Bladder Epithelial Cytotoxicity

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Mode of Action of Pulegone on the Urinary Bladder of F344 Rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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

Extracts of the spice ginger (Zingiber officinale Roscoe) are rich in gingerols and shogaols, which exhibit antioxidant, anti-inflammatory, antifungal, anti mycobacterial, 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 reficulocytes 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.

Estrogen metabolites for the diagnosis of schistosomiasis associated urinary bladder cancer

Letter to the Editor

Challenges with in vitro and in vivo experimental models of urinary bladder cancer for novel drug discovery

Urinary bladder cancer (UBC) is the second most frequent malignancy of the urinary system and the ninth most common cancer worldwide, affecting individuals over the age of 65. Several investigations have embarked on advancing knowledge of the mechanisms underlying urothelial carcinogenesis, understanding the mechanisms of antineoplastic drugs resistance and discovering new antineoplastic drugs. In vitro and in vivo models are crucial for providing additional insights into the mechanisms of urothelial carcinogenesis. With these models, various molecular pathways involved in urothelial carcinogenesis have been discovered, allowing therapeutic manipulation.

Interstitial Cells in the Urinary Bladder-Localization and Function

Aims: This review summarizes the currently available literature on the localization and proposed functions of a novel group of cells in the urinary bladder known as interstitial cells or interstitial cells of Cajal (ICC).

Methods: On-line searches of "Pubmed" for bladder, c-Kit, ICC, interstitial cell and myofibroblast were performed to identify relevant studies for the review.

Results: The literature contains substantial data that several sub-populations of ICC are present in the wall of the mammalian urinary bladder. These are located in the lamina propria and within the detrusor with distinctive cell shapes and morphological arrangements. Bladder ICC are identified with transmission electron microscopy or by immunohistochemical labeling using antibodies to the Kit receptor which is an established ICC marker. Lamina propria-ICC form a loose network connected via Cx43 gap junctions and are associated with mucosal nerves. Detrusor ICC track the smooth muscle bundles and make frequent contacts with intramural nerves. Both groups of ICC exhibit spontaneous electrical and Ca²⁺-signalling and also respond to application of neurotransmitter substances including ATP and carbachol. There is emerging evidence that the expression of ICC is upregulated in pathophysiological conditions including the overactive bladder.

Conclusions: There is now a convincing body of evidence that specialized ICC are present in the urinary bladder making important associations with other cells that make up the bladder wall and possessing physiological properties consistent with a role of bladder activity modulation. Neurourol. Urodynam. 29: 82–87, 2010. © 2009 Wiley-Liss, Inc.

Preconditioning protects the guinea-pig urinary bladder against ischaemic conditions in vitro

Aims: To investigate the ability of ischaemic preconditioning (IPC) to protect guinea-pig detrusor from damage caused by a subsequent more prolonged exposure to ischaemic conditions.

Materials and Methods: Smooth muscle strips were mounted for tension recording in small organ baths continuously superfused with Krebs' solution at 37 degrees C. Ischaemia was mimicked by removing oxygen and glucose from the superfusing solution. Contractile responses to electrical field stimulation (EFS) and carbachol were monitored. Three regimes of preconditioning were examined: 15, 10, and 5 min of ischaemic conditions followed by 15, 10, and 5 min of normal conditions, respectively.

Results: Without preconditioning, nerve-mediated responses were significantly and proportionally reduced by periods of ischaemic conditions lasting for 45, 60, and 90 min, but recovered fully after exposure to ischaemic conditions for 30 min. The recovery of the responses to EFS was significantly improved in preconditioned strips when the period of ischaemic conditions was 45 or 60 min. However, no significant differences were seen with preconditioning when the period of ischaemic conditions was 90 min. The recovery of responses to carbachol was much greater than for the responses to EFS, and no significant differences were found between control and preconditioned strips.

Conclusions: It is suggested that in vivo short periods of transient ischaemia may be able to protect the guinea-pig bladder from the impairment associated with longer periods of ischaemia and reperfusion, which might happen in obstructed micturition. Our results also indicate that the phenomenon affects mainly the intrinsic nerves, which are more susceptible to ischaemic damage than the smooth muscle.

Natriuretic peptide regulation of the kidney and urinary bladder in the cane toad, Bufo marinus

The natriuretic peptide system of mammals is important in the control of blood volume but its function in non-mammalian animals is unclear. This study identified a functional natriuretic peptide system in an amphibian and showed that the hormones are involved in the control of fluid balance.

DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)