Effect of sodium saccharin and calcium saccharin on urinary parameters in rats fed Prolab 3200 or AIN-76 diet

Fisher, Maria J.; Sakata, Takao; Tibbels, T. Scott; Smith, Raymond A.; Patil, Kashinath D.; Khachab, M.; Johansson, Sonny L.; Cohen, Samuel M.

doi:10.1016/0278-6915(89)90085-9

Cited by 33 publications

(13 citation statements)

References 16 publications

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“…Our laboratory has been investigating various urinary parameters influencing the carcinogenic process in the bladder produced by a variety of genotoxic and nongenotoxic chemicals (1,5,6). Early changes in the urothelium have been examined by light and scanning electron microscopy along with cell kinetic studies utilizing tritiated thymidine or bromodeoxyuridine labeling (3).…”

Section: Introductionmentioning

confidence: 99%

“…Although 24-hr urine collections can provide some important and useful data, in some circumstances it appears such collections can produce somewhat misleading results. This is particularly true for many of the critical chemical changes that follow a diurnal pattern related to the timing of food and water consumption (1,6), which in rodents is primarily during the dark hours. To differences in water consumption between rats that were frequently handled and those with minimal handling.…”

Section: Introductionmentioning

confidence: 99%

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Extensive Handling of Rats Leads to Mild Urinary Bladder Hyperplasia

et al. 1996

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The urinary and urothelial effects of the frequent handling necessary for obtaining fresh-voided urine specimens were evaluated in 5-wk-old male F-344 rats fed control diet or diet containing 7.5% sodium saccharin. Frequent handling consisted of holding rats by the back of the neck in a position to obtain fresh-voided urine directly into centrifuge tubes 3 times per week for 10 weeks, whereas seldomly handled control rats received this treatment only twice during the entire 10 weeks. The urothelium of frequently handled rats fed control diet showed superficial necrosis and regenerative hyperplasia as observed by light and scanning electron microscopy. These changes were not observed in rats fed control diet that were seldomly handled. The necrosis and hyperplasia were not as pronounced in frequently handled rats fed control diet as in seldomly handled, sodium-saccharin-treated rats, but handling also potentiated the severity of the changes produced by sodium saccharin feeding. The urothelial exfoliation and consequent regenerative hyperplasia are likely secondary effects of stress.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Extensive Handling of Rats Leads to Mild Urinary Bladder Hyperplasia

et al. 1996

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“…Because of these dynamic variations in the organism as a whole, the composition of urine can vary markedly during a 24-hour period (Fisher et al, 1989;Cohen, 1995). Since urine composition reflects food and water consumption most closely, it is not surprising that there is a distinct diurnal variation in its composition.…”

Section: Introductionmentioning

confidence: 99%

“…They discontinue eating and drinking when lights come on in the animal room in the morning and sleep during the daylight hours (Fisher et al, 1989;Cohen, 1995). These dietary habits produce dramatic changes in the urinary composition.…”

Section: Introductionmentioning

confidence: 99%

Investigations of Rodent Urinary Bladder Carcinogens: Collection, Processing, and Evaluation of Urine and Bladders

et al. 2007

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Examination of the urine and the bladder epithelium are essential to the investigation of mechanisms of urinary bladder carcinogens in rodents. However, urine and bladder tissue specimens must be collected and processed properly if accurate data are to be derived. The optimum specimen for analysis of urinary constituents is fresh void urine collected from nonfasting animals. Fasting the animal prior to urine collection changes the normal composition, including pH. Many of the normal urinary constituents can influence the mode of action of bladder carcinogens, especially for non-genotoxic agents. Light microscopy is routinely used to examine the bladder epithelium. However, it is often necessary to use more sensitive techniques, such as scanning electron microscopy (SEM) to detect subtle cytotoxic changes in the superficial cell layer of the urothelium, and bromodeoxyuridine (BrdU) incorporation, PCNA, or Ki-67 immunohistochemistry to determine the labeling index for cell proliferation. The urinary bladder must be handled gently and inflated with fixative in situ before the animal dies to avoid artifactual autolytic damage to the bladder epithelium that is visible by SEM and may be mistaken for treatment-related changes. The purpose of this paper is to provide information for the proper collection and examination of urine and the urinary bladder.

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“…As to the sex difference, male rodents are frequently affected to a greater extent than females. Several factors including potential hormonal effects and total amounts of specific types of urinary proteins have been suggested for this difference [25,27,29,30,31].…”

Section: Factors Affecting Calculus Formationmentioning

confidence: 99%