Tumorigenicity of sodium ascorbate in male rats

Samuel Monroe Cohen, Traci A. Anderson, Louisa Maria De Oliveira, Lora L Arnold

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Sodium ascorbate, like other sodium salts such as saccharin, glutamate, and bicarbonate, produces urinary alterations when fed at high doses to rats, which results in mild superficial urothelial cytotoxicity and regeneration but not tumors in a standard 2-year bioassay. Sodium saccharin was shown to produce a low incidence of bladder tumors in rats if administered in a two- generation bioassay. In the present study, we evaluated sodium ascorbate in a two-generation bioassay that involved feeding to the male and female parental F344 rats for 4 weeks before mating, feeding the dams during gestation and lactation, and then feeding the weaned (at 28 days of age) male F1 generation rats for the remainder of their lifetime (up to 128 weeks of the experiment). Dietary levels of 1.0, 5.0, and 7.0% sodium ascorbate were tested. At 5.0 and 7.0% sodium ascorbate, there was an increase in urinary bladder urothelial papillary and nodular hyperplasia and the induction of a few papillomas and carcinomas. There was a dose-responsive increase in renal pelvic calcification and hyperplasia and inhibition of the aging nephropathy of rats even at the level of 1% sodium ascorbate. Because the short-term urothelial effects of sodium ascorbate in rats are inhibited by treatments producing urinary acidification to pH < 6.0, we coadministered high doses of long-term NH4Cl to groups of rats with 5.0 or 7.0% sodium ascorbate to evaluate the long-term effects. The combination of 7.0% sodium ascorbate plus 2.78% NH4Cl in the diet was toxic, and the group was terminated early during the course of the experiment. The group fed 5.0% sodium ascorbate plus 2.04% NH4Cl showed complete inhibition of the urothelial effects of sodium ascorbate and significant inhibition of its renal effects. We also demonstrated the presence of a calcium phosphate-containing urinary precipitate in rats fed sodium ascorbate at all doses, in a dose-responsive manner. The formation of the precipitate was inhibited by coadministration with NH4Cl. The proliferative effects of sodium ascorbate on the male rat urinary tract in this study are similar to those seen with sodium saccharin when administered in a two-generation bioassay. Mechanistic information suggests that this is a high-dose, rat-specific phenomenon.

Original languageEnglish (US)
Pages (from-to)2557-2561
Number of pages5
JournalCancer Research
Volume58
Issue number12
StatePublished - Jun 15 1998

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Ascorbic Acid
Saccharin
Biological Assay
Hyperplasia
Kidney
Poisons
Inbred F344 Rats
Papilloma
Bicarbonates
Urinary Tract
Lactation
Urinary Bladder Neoplasms
Regeneration
Glutamic Acid
Urinary Bladder
Salts
Sodium
Diet
Carcinoma
Pregnancy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Cohen, S. M., Anderson, T. A., De Oliveira, L. M., & Arnold, L. L. (1998). Tumorigenicity of sodium ascorbate in male rats. Cancer Research, 58(12), 2557-2561.

Tumorigenicity of sodium ascorbate in male rats. / Cohen, Samuel Monroe; Anderson, Traci A.; De Oliveira, Louisa Maria; Arnold, Lora L.

In: Cancer Research, Vol. 58, No. 12, 15.06.1998, p. 2557-2561.

Research output: Contribution to journalArticle

Cohen, SM, Anderson, TA, De Oliveira, LM & Arnold, LL 1998, 'Tumorigenicity of sodium ascorbate in male rats', Cancer Research, vol. 58, no. 12, pp. 2557-2561.
Cohen SM, Anderson TA, De Oliveira LM, Arnold LL. Tumorigenicity of sodium ascorbate in male rats. Cancer Research. 1998 Jun 15;58(12):2557-2561.
Cohen, Samuel Monroe ; Anderson, Traci A. ; De Oliveira, Louisa Maria ; Arnold, Lora L. / Tumorigenicity of sodium ascorbate in male rats. In: Cancer Research. 1998 ; Vol. 58, No. 12. pp. 2557-2561.
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abstract = "Sodium ascorbate, like other sodium salts such as saccharin, glutamate, and bicarbonate, produces urinary alterations when fed at high doses to rats, which results in mild superficial urothelial cytotoxicity and regeneration but not tumors in a standard 2-year bioassay. Sodium saccharin was shown to produce a low incidence of bladder tumors in rats if administered in a two- generation bioassay. In the present study, we evaluated sodium ascorbate in a two-generation bioassay that involved feeding to the male and female parental F344 rats for 4 weeks before mating, feeding the dams during gestation and lactation, and then feeding the weaned (at 28 days of age) male F1 generation rats for the remainder of their lifetime (up to 128 weeks of the experiment). Dietary levels of 1.0, 5.0, and 7.0{\%} sodium ascorbate were tested. At 5.0 and 7.0{\%} sodium ascorbate, there was an increase in urinary bladder urothelial papillary and nodular hyperplasia and the induction of a few papillomas and carcinomas. There was a dose-responsive increase in renal pelvic calcification and hyperplasia and inhibition of the aging nephropathy of rats even at the level of 1{\%} sodium ascorbate. Because the short-term urothelial effects of sodium ascorbate in rats are inhibited by treatments producing urinary acidification to pH < 6.0, we coadministered high doses of long-term NH4Cl to groups of rats with 5.0 or 7.0{\%} sodium ascorbate to evaluate the long-term effects. The combination of 7.0{\%} sodium ascorbate plus 2.78{\%} NH4Cl in the diet was toxic, and the group was terminated early during the course of the experiment. The group fed 5.0{\%} sodium ascorbate plus 2.04{\%} NH4Cl showed complete inhibition of the urothelial effects of sodium ascorbate and significant inhibition of its renal effects. We also demonstrated the presence of a calcium phosphate-containing urinary precipitate in rats fed sodium ascorbate at all doses, in a dose-responsive manner. The formation of the precipitate was inhibited by coadministration with NH4Cl. The proliferative effects of sodium ascorbate on the male rat urinary tract in this study are similar to those seen with sodium saccharin when administered in a two-generation bioassay. Mechanistic information suggests that this is a high-dose, rat-specific phenomenon.",
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