sodium-bicarbonate and Hyperplasia

The effect of terephthalic acid (TPA) on urinary bladder carcinogenesis was examined. Male Wistar rats were initiated by injection of N-Methyl-N-Nitrosourea (MNU) (20 mg/kg b.w. ip) twice a week for 4 weeks, then given basal diet containing 5% TPA, 5% TPA plus 4% Sodium bicarbonate (NaHCO3) or 1% TPA for the next 22 weeks, and then euthanized. 5% TPA treatment induced a high incidence of urinary bladder calculi and a large amount of precipitate. Though 5% TPA plus 4% Sodium bicarbonate (NaHCO3) and 1% TPA treatment did not induce urinary bladder calculi formation, they resulted in a moderate increase in urinary precipitate. Histological examination of urinary bladder revealed that MNU-5% TPA treatment resulted in a higher incidence of simple hyperplasia, papillary or nodular hyperplasia (PN hyperplasia), papilloma and cancer than MNU control. MNU-5% TPA plus 4% Sodium bicarbonate (NaHCO3) and 1% TPA treatment increased slightly the incidence of simple hyperplasia and PN hyperplasia (not statistically significant). The major elements of the precipitate are phosphorus, potassium, sulfur, chloride, calcium and TPA. The present study indicated that the calculi induced by TPA had a strong promoting activity on urinary bladder carcinogenesis and the precipitate containing calcium terephthalate (CaTPA) may also have weak promoting activity on urinary bladder carcinogenesis.

Topics: Animals; Carcinogenicity Tests; Cocarcinogenesis; Dose-Response Relationship, Drug; Hyperplasia; Male; Methylnitrosourea; Microscopy, Electron, Scanning; Phthalic Acids; Rats; Rats, Wistar; Sodium Bicarbonate; Urinalysis; Urinary Bladder; Urinary Bladder Calculi; Urinary Bladder Neoplasms

Urinary bladder hyperplasia associated with terephthalic acid (TPA) treatment was examined with concomitant use of sodium bicarbonate (NaHCO3) or hydrochlorothiazide to allow assessment of the relationship among bladder stones, epithelial hyperplasia, and corresponding cell cycle checkpoint gene expression in Sprague-Dawley (SD) rat.. A total of 112 weanling male SD rats that divided between six groups were given basal diet (control), diets containing 5% TPA or in combination with either 4% sodium NaHCO3 or 0.02% hydrochlorothiazide. After 90-day feeding, bladder samples were collected for histopathological diagnoses, and immunohistochemical method was used to characterize the expression of p16Ink4a cyclin D1, CDK4, EGFr and cyclin E in relation to that of proliferating cell nuclear antigen (PCNA).. In TPA treatment groups, bladder stone incidence was 40% (21/52) with 14 cases of proliferative bladder. In control and other groups, neither stone nor epithelial cell proliferation was diagnosed. PCNA-positive focal hyperplasic lesions involved all epithelial layers. Overexpressions of cyclin D1, CDK4, EGFr are found in the corresponding lesion. p16Ink4a nuclear staining reduced in proliferative bladders especially with a great quantity of stone. In addition, no positive expression was detected on cyclin E.. The present study provides a strong evidence of a link between induction of bladder hyperplasia, deregulation of the p16Ink4a-cyclin D1/CDK4 pathway, and abnormal EGFr mediated signal transduction pathway.

Topics: Animals; Cell Division; Cocarcinogenesis; Cyclin D1; Cyclin E; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinases; Epithelial Cells; ErbB Receptors; Free Radical Scavengers; G1 Phase; Hydrochlorothiazide; Hyperplasia; Immunohistochemistry; Male; Phthalic Acids; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins; Random Allocation; Rats; Rats, Sprague-Dawley; S Phase; Sodium Bicarbonate; Urinary Bladder; Urinary Bladder Calculi

The role of urinary pH and Na+ concentration on the bladder carcinogenesis of o-phenylphenol (OPP) was examined in male F344 rats. The rats were given powdered diet containing 2% sodium o-phenylphenate (OPP-Na, group 1), 1.25% OPP plus 0.64% NaHCO3 (group 2), 1.25% OPP plus 0.32% NaHCO3 (group 3), 1.25% OPP plus 0.16% NaHCO3 (group 4), 1.25% OPP (group 5), 0.64% NaHCO3 (group 6) or no test chemical (group 7) for 104 weeks respectively. Incidences of bladder carcinoma induced were significantly higher in groups 1 (12 of 29 rats, 41.4%) and 2 (9 of 29 rats, 31.0%) than in group 7 (0 of 27 rats, 0%). Groups 3 and 4 induced bladder carcinomas in 4 of 29 rats (13.8%) and 4 of 26 rats (15.4%) respectively, whereas no tumors occurred in group 5 (0 of 27, 0%). The incidence in group 6 was 3.6% (1 of 28 rats). Groups 1 and 2 induced significant increases in urinary pH and Na+ concentrations, whereas group 5 did not. Groups 3 and 4 showed the same tendency as groups 1 and 2. Examination with a scanning electron microscope showed the appearance of pleomorphic microvilli, short, uniform microvilli, and ropy or leafy microridges on the luminal surface of the bladder in groups 1-5 of rats treated with OPP or OPP-Na for 8 weeks. The appearance and severity were the same in groups 1 and 2, followed by the groups with decreasing doses of NaHCO3. The results indicated that OPP-Na is carcinogenic for the rat bladder, but OPP is not. However, increased urinary pH and Na+ concentration play important roles in OPP-Na rat bladder carcinogenesis.

Topics: Animals; Bicarbonates; Biphenyl Compounds; Carcinogens; Carcinoma; Fungicides, Industrial; Hydrogen-Ion Concentration; Hyperplasia; Male; Papilloma; Rats; Rats, Inbred F344; Sodium; Sodium Bicarbonate; Urinary Bladder; Urinary Bladder Neoplasms; Urine

The promoting activities of low and high sodium or potassium ion concentrations, under conditions of neutral as well as elevated urinary pH, in urinary bladder carcinogenesis, were investigated in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Male Wistar rats were given 0.05% BBN in their drinking water for 4 weeks and then treated for 32 weeks with either control diet (group 1) or this diet supplemented with equimolar amounts of the following minerals: 2.34% NaCl (group 2), 2.98% KCl (group 3), 3.36% NaHCO3 (group 4), 1.68% NaHCO3 + 2% KHCO3 (group 5), or 4% KHCO3 (group 6). The alkalizing salts NaHCO3 and KHCO3 induced comparable increases in urinary pH and elevated urinary sodium or potassium ion concentrations respectively. The combination of NaHCO3 + KHCO3 similarly caused an elevation of the urinary pH and less increased sodium and potassium ion concentrations. In the groups fed NaHCO3 and KHCO3 either alone or in combination, the incidences of papillary/nodular hyperplasia, papillomas and carcinomas in the urinary bladder had increased as compared to controls. NaCl and KCl also induced high urinary sodium or potassium ion concentrations without alteration of urinary pH. This was accompanied by increased incidences of simple hyperplasia, papillary/nodular hyperplasia, and/or papillomas but no carcinomas. The present results indicate that the potassium ion is as potent as the sodium ion in promoting urinary bladder carcinogenesis under conditions of elevated urinary pH, and that both the sodium and potassium ions may exert weak promoting activity under conditions of neutral urinary pH.

Topics: Animals; Bicarbonates; Butylhydroxybutylnitrosamine; Carcinogens; Hydrogen-Ion Concentration; Hyperplasia; Male; Nitrosamines; Papilloma; Potassium; Rats; Rats, Inbred Strains; Sodium; Sodium Bicarbonate; Urinary Bladder; Urinary Bladder Neoplasms