Bladder freeze ulceration and sodium saccharin feeding in the rat

Examination for urinary nitrosamines, mutagens and bacteria, and effects on hepatic microsomal enzymes

R. Hasegawa, M. K St John, M. Cano, P. Issenberg, D. A. Klein, B. A. Walker, J. W. Jones, R. C. Schnell, B. A. Merrick, M. H. Davies, D. T. McMillan, Samuel Monroe Cohen

Research output: Contribution to journalArticle

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Abstract

We previously demonstrated that long-term feeding of sodium saccharin, a non-mutagen, induced bladder carcinomas when administered to F344 male rats with regenerative hyperplasia of the urothelium induced by the freeze-ulceration technique, even without prior chemical initiation (Cohen et al. Cancer Res. 1982, 42, 65). In the present study, we examined the urine of rats subjected to freeze ulceration of the bladder and then fed sodium saccharin at 5% in the diet to evaluate the possibility of a mutagen being generated as a result of ulceration and/or saccharin feeding. Urine was collected into a syringe by aspiration from the urinary bladder after ligating the urethra for 2 hr at intervals from day 0 to day 14 after ulceration. After ulceration and/or sodium saccharin feeding, the urine showed no bacterial contamination, no mutagenic activity in the standard Ames assay, no production of nitrosamines, and no nitrosating environment. In addition, no significant changes in activities of liver microsomal enzymes (i.e. cytochrome P-450, NADPH-cytochrome c reductase, aniline hydroxylase, or ethylmorphine N-demethylase) were observed in rats fed sodium saccharin for 1, 5 or 14 days. Thus, freeze ulceration, and the consequent regenerative hyperplasia of the epithelium, compared with sodium saccharin feeding do not involve the administration of an exogenous mutagenic substance or the generation of a detectable mutagen in the urine.

Original languageEnglish (US)
Pages (from-to)935-942
Number of pages8
JournalFood and Chemical Toxicology
Volume22
Issue number12
DOIs
StatePublished - Jan 1 1984

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nitrosamines
saccharin
Saccharin
Nitrosamines
Mutagens
bladder
Rats
Bacteria
Urinary Bladder
sodium
liver
Liver
bacteria
rats
urine
Enzymes
enzymes
Urine
hyperplasia
Hyperplasia

ASJC Scopus subject areas

  • Food Science
  • Toxicology

Cite this

Bladder freeze ulceration and sodium saccharin feeding in the rat : Examination for urinary nitrosamines, mutagens and bacteria, and effects on hepatic microsomal enzymes. / Hasegawa, R.; John, M. K St; Cano, M.; Issenberg, P.; Klein, D. A.; Walker, B. A.; Jones, J. W.; Schnell, R. C.; Merrick, B. A.; Davies, M. H.; McMillan, D. T.; Cohen, Samuel Monroe.

In: Food and Chemical Toxicology, Vol. 22, No. 12, 01.01.1984, p. 935-942.

Research output: Contribution to journalArticle

Hasegawa, R, John, MKS, Cano, M, Issenberg, P, Klein, DA, Walker, BA, Jones, JW, Schnell, RC, Merrick, BA, Davies, MH, McMillan, DT & Cohen, SM 1984, 'Bladder freeze ulceration and sodium saccharin feeding in the rat: Examination for urinary nitrosamines, mutagens and bacteria, and effects on hepatic microsomal enzymes', Food and Chemical Toxicology, vol. 22, no. 12, pp. 935-942. https://doi.org/10.1016/0278-6915(84)90142-X
Hasegawa, R. ; John, M. K St ; Cano, M. ; Issenberg, P. ; Klein, D. A. ; Walker, B. A. ; Jones, J. W. ; Schnell, R. C. ; Merrick, B. A. ; Davies, M. H. ; McMillan, D. T. ; Cohen, Samuel Monroe. / Bladder freeze ulceration and sodium saccharin feeding in the rat : Examination for urinary nitrosamines, mutagens and bacteria, and effects on hepatic microsomal enzymes. In: Food and Chemical Toxicology. 1984 ; Vol. 22, No. 12. pp. 935-942.
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abstract = "We previously demonstrated that long-term feeding of sodium saccharin, a non-mutagen, induced bladder carcinomas when administered to F344 male rats with regenerative hyperplasia of the urothelium induced by the freeze-ulceration technique, even without prior chemical initiation (Cohen et al. Cancer Res. 1982, 42, 65). In the present study, we examined the urine of rats subjected to freeze ulceration of the bladder and then fed sodium saccharin at 5{\%} in the diet to evaluate the possibility of a mutagen being generated as a result of ulceration and/or saccharin feeding. Urine was collected into a syringe by aspiration from the urinary bladder after ligating the urethra for 2 hr at intervals from day 0 to day 14 after ulceration. After ulceration and/or sodium saccharin feeding, the urine showed no bacterial contamination, no mutagenic activity in the standard Ames assay, no production of nitrosamines, and no nitrosating environment. In addition, no significant changes in activities of liver microsomal enzymes (i.e. cytochrome P-450, NADPH-cytochrome c reductase, aniline hydroxylase, or ethylmorphine N-demethylase) were observed in rats fed sodium saccharin for 1, 5 or 14 days. Thus, freeze ulceration, and the consequent regenerative hyperplasia of the epithelium, compared with sodium saccharin feeding do not involve the administration of an exogenous mutagenic substance or the generation of a detectable mutagen in the urine.",
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T2 - Examination for urinary nitrosamines, mutagens and bacteria, and effects on hepatic microsomal enzymes

AU - Hasegawa, R.

AU - John, M. K St

AU - Cano, M.

AU - Issenberg, P.

AU - Klein, D. A.

AU - Walker, B. A.

AU - Jones, J. W.

AU - Schnell, R. C.

AU - Merrick, B. A.

AU - Davies, M. H.

AU - McMillan, D. T.

AU - Cohen, Samuel Monroe

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N2 - We previously demonstrated that long-term feeding of sodium saccharin, a non-mutagen, induced bladder carcinomas when administered to F344 male rats with regenerative hyperplasia of the urothelium induced by the freeze-ulceration technique, even without prior chemical initiation (Cohen et al. Cancer Res. 1982, 42, 65). In the present study, we examined the urine of rats subjected to freeze ulceration of the bladder and then fed sodium saccharin at 5% in the diet to evaluate the possibility of a mutagen being generated as a result of ulceration and/or saccharin feeding. Urine was collected into a syringe by aspiration from the urinary bladder after ligating the urethra for 2 hr at intervals from day 0 to day 14 after ulceration. After ulceration and/or sodium saccharin feeding, the urine showed no bacterial contamination, no mutagenic activity in the standard Ames assay, no production of nitrosamines, and no nitrosating environment. In addition, no significant changes in activities of liver microsomal enzymes (i.e. cytochrome P-450, NADPH-cytochrome c reductase, aniline hydroxylase, or ethylmorphine N-demethylase) were observed in rats fed sodium saccharin for 1, 5 or 14 days. Thus, freeze ulceration, and the consequent regenerative hyperplasia of the epithelium, compared with sodium saccharin feeding do not involve the administration of an exogenous mutagenic substance or the generation of a detectable mutagen in the urine.

AB - We previously demonstrated that long-term feeding of sodium saccharin, a non-mutagen, induced bladder carcinomas when administered to F344 male rats with regenerative hyperplasia of the urothelium induced by the freeze-ulceration technique, even without prior chemical initiation (Cohen et al. Cancer Res. 1982, 42, 65). In the present study, we examined the urine of rats subjected to freeze ulceration of the bladder and then fed sodium saccharin at 5% in the diet to evaluate the possibility of a mutagen being generated as a result of ulceration and/or saccharin feeding. Urine was collected into a syringe by aspiration from the urinary bladder after ligating the urethra for 2 hr at intervals from day 0 to day 14 after ulceration. After ulceration and/or sodium saccharin feeding, the urine showed no bacterial contamination, no mutagenic activity in the standard Ames assay, no production of nitrosamines, and no nitrosating environment. In addition, no significant changes in activities of liver microsomal enzymes (i.e. cytochrome P-450, NADPH-cytochrome c reductase, aniline hydroxylase, or ethylmorphine N-demethylase) were observed in rats fed sodium saccharin for 1, 5 or 14 days. Thus, freeze ulceration, and the consequent regenerative hyperplasia of the epithelium, compared with sodium saccharin feeding do not involve the administration of an exogenous mutagenic substance or the generation of a detectable mutagen in the urine.

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