Extensive Handling of Rats Leads to Mild Urinary Bladder Hyperplasia

Cohen, Samuel M.; Cano, Martín; Anderson, Traci; Garland, Emily M.

doi:10.1177/019262339602400214

Cited by 19 publications

(10 citation statements)

References 8 publications

(6 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, handling of the hamsters was kept to a minimum. It has been demonstrated in rats and mice that excessive stress to the animals can lead to similar kinds of changes in urothelium as seen in this present dietary study in hamsters (6). The hamsters were handled identically in all groups, so that the differences between groups obviously cannot be explained on the basis of handling stress.…”

Section: Discussionsupporting

confidence: 59%

“…The kidneys were removed, weighed, and placed in formalin. One half of the bladder from each animal was processed for examination by SEM and classi ed as previously described (6). The other half of the bladder was cut longitudinally into strips, and with a slice of stomach, was embedded in parafn, stained with hematoxylin and eosin (H&E) and examined histopathologically (4,7).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of Diet and Dimethylarsinic Acid on the Urothelium of Syrian Golden Hamsters

2001

Self Cite

View full text Add to dashboard Cite

Few studies have examined the carcinogenicity of chemicals toward the urinary bladder in hamsters, and the effect of diet on hamster urine and urothelium has not been reported. Our laboratory recently began investigating the effects of dimethylarsinic acid (DMA) on the hamster bladder, and we noticed subtle urothelial changes even in controls. The possible effect of various diets on hamster urothelium was evaluated by feeding different diets to 4-week-old Syrian Golden hamsters for 5 weeks. The diets examined were Tekland 8656, Purina 5002, Purina 5L79, and NIH-07. Light microscopic examination showed a slight increase in urothelial hyperplasia in hamsters fed Purina 5L79. An increase in the incidence of urinary bladder necrosis, exfoliation, and mild hyperplasia were noted by scanning electron microscopy (SEM) with all dietary preparations except NIH-07. The constituents in the diets producing the urothelial alterations are not known at present, but NIH-07 diet was chosen for experiments to investigate the effects of DMA on the hamster bladder epithelium. Male and female 5-week-old Syrian Golden hamsters were fed 100 ppm DMA for 10 weeks. Examination of urinary parameters showed no treatment-related changes. Light microscopic examination and SEM revealed no changes of the urothelium of DMA-treated male or female hamsters.

show abstract

Section: Discussionsupporting

confidence: 59%

Section: Methodsmentioning

confidence: 99%

Evaluation of Diet and Dimethylarsinic Acid on the Urothelium of Syrian Golden Hamsters

2001

Self Cite

View full text Add to dashboard Cite

show abstract

“…Fresh-voided urine and 24-h urine were collected during different study weeks to avoid excessive handling of the rats on any given day. Excessive handling produces urothelial hyperplasia by itself (Cohen et al, 1996). Food and water were available ad libitum while the rats were in the metabolism cages.…”

Section: Methodsmentioning

confidence: 99%

Urothelial Cytotoxicity and Regeneration Induced by Dimethylarsinic Acid in Rats

Cohen

Yamamoto

Cano

et al. 2001

Toxicological Sciences

View full text Add to dashboard Cite

Inorganic arsenic is a known human carcinogen of the skin and respiratory tract. Epidemiologic evidence indicates that it is also carcinogenic to the urinary bladder and other internal organs. Lack of an animal model has limited progress on understanding the mechanism of arsenic carcinogenesis. It was recently reported that high doses of an organic arsenical, dimethylarsinic acid (DMA), increased urinary bladder tumors in rats when administered in the diet or in the drinking water for 2 years, with the female being more sensitive than the male. We previously showed that high doses of DMA (40 or 100 ppm of the diet) fed for 10 weeks increased urothelial cell proliferation in the rat. Treatment with DMA also increased renal calcification and increased urinary calcium concentration. In 2 experiments, we examined the urothelial proliferative effects of treatment with 100 ppm DMA in the diet in female F344 rats for 2 and 10 weeks and for 6 and 24 h, and 3, 7, and 14 days. Cytotoxic changes in the urothelium were evident by SEM as early as 6 h after treatment was begun. Foci of cellular necrosis were detected after 3 days of treatment, followed by widespread necrosis of the urothelium after 7 days of treatment. The bromodeoxyuridine (BrdU) labeling index was not increased until after 7 days of treatment, suggesting that administration of DMA results in cytotoxicity with necrosis, followed by regenerative hyperplasia of the bladder epithelium. Although the rat provides an animal model to study the urothelial effects of DMA, the relevance of this finding to inorganic arsenic carcinogenesis in humans must be extrapolated cautiously, due to the high doses of DMA necessary to produce these changes in the rat and the differences in metabolism of arsenicals in rodents, especially rats, compared to humans.

show abstract

“…Hyperplasia must be carefully distinguished from an apparent increased cellularity secondary to folding and/or tangential sectioning when the bladder is fixed in a nondistended state. Hyperplasia has also been reported as a consequence of extensive handling in rats (Cohen et al 1996). Hyperplasia often appears to extend downward into the submucosa, resulting from chronic cystitis (Shinohara and Frith 1981).…”

Section: Differential Diagnosesmentioning

confidence: 99%

Proliferative and Nonproliferative Lesions of the Rat and Mouse Urinary System

et al. 2012

View full text Add to dashboard Cite

The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying lesions observed in the urinary tract of rats and mice. The standardized nomenclature of urinary tract lesions presented in this document is also available electronically on the Internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous developmental and aging lesions as well as those induced by exposure to test materials. A widely accepted and utilized international harmonization of nomenclature for urinary tract lesions in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists.

show abstract

Extensive Handling of Rats Leads to Mild Urinary Bladder Hyperplasia

Cited by 19 publications

References 8 publications

Evaluation of Diet and Dimethylarsinic Acid on the Urothelium of Syrian Golden Hamsters

Evaluation of Diet and Dimethylarsinic Acid on the Urothelium of Syrian Golden Hamsters

Urothelial Cytotoxicity and Regeneration Induced by Dimethylarsinic Acid in Rats

Proliferative and Nonproliferative Lesions of the Rat and Mouse Urinary System

Contact Info

Product

Resources

About