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Chemical Compound Review

saccharin     9,9-dioxo-9$l^{6}-thia-8...

Synonyms: Kandiset, Madhurin, Sacarina, Sacharin, Sucrette, ...
 
 
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Disease relevance of SACCHARIN SODIUM

  • The risk of a person getting cancer from ingesting saccharin is compared with the risk of ingesting additional calories which cause excess body weight [1].
  • Highly purified saccharin was not mutagenic in the direct assay, but the urines of mice to which this material had been administered exhibited mutagenic effects on one tester strain (Salmonella typhimurium TA100) [2].
  • The rate of development of proteinuria and mortality were significantly retarded in these conditioned mice relative to untreated controls and nonconditioned animals that received unpaired treatment with saccharin and cyclophosphamide [3].
  • In the presence of saccharin, hyperplasia induced by a single dose of MNU persisted [4].
  • No increase in incidence of papilloma or cancer was noted in either sex at any dose of saccharin after BBN as compared to levels induced by BBN alone [5].
 

Psychiatry related information on SACCHARIN SODIUM

  • Factors examined and not found to be related to pancreatic cancer included education, occupation, religion, marital status, alcohol drinking, saccharin use, height, weight 5 years before hospitalization, history of previous diseases, and residence [6].
  • The high-ethanol preferring line of rats used is characterized by a: (i) high voluntary consumption of alcohol; (ii) high sensitivity to taste reinforcement (saccharine, quinine); (iii) high locomotor activity in a novel environment; and (iv) low emotional reactivity, these features being opposite in the Wistar-Kyoto (WKY) rat strain [7].
  • There were no differences when saccharin was presented to naive animals, indicating that the different ethanol drinking behavior of HAB and LAB rats does not represent a general difference in the consumption of new liquids [8].
  • In this study, patients with schizophrenia, healthy control subjects, and controls with bipolar affective disorder were tested using double-blind treatment with either 50 g anhydrous dextrose plus 4 mg sodium saccharin (for "taste") or 23.7 mg saccharin alone, followed by cognitive testing on a complex battery [9].
  • Both naloxone (3 and 10 mg X kg-1) and naltrexone (1-10 mg X kg-1) abolished the preference for a highly palatable 0.05% sodium saccharin solution in rats that had been adapted to a 22 hr water-deprivation schedule [10].
 

High impact information on SACCHARIN SODIUM

  • The Sac locus in mouse, mapped to the distal end of chromosome 4 (refs. 7-9), is the major determinant of differences between sweet-sensitive and -insensitive strains of mice in their responsiveness to saccharin, sucrose and other sweeteners [11].
  • We report here a series of experiments demonstrating the elimination of metabolic cooperation in the hypoxanthine guanine phosphoribosyltransferase (HGPRT) system in Chinese hamster V79 cells, indicating that saccharin shares properties similar to those of other known promoters [12].
  • Many of these nongenotoxic compounds (such as sodium saccharin) have in common the property that they increase cell proliferation in the target organ [13].
  • Calcitonin did not produce a conditioned taste aversion to saccharin, and maximum inhibition of feeding occurred 4.5 to 8.3 hours after subcutaneous administration [14].
  • At each test dose, cells grown in impure saccharin exhibited up to sevenfold higher frequencies of mitotic crossing-over or gene conversion in three of four assays for genetic recombination than cells grown in purified saccharin from the same lot [15].
 

Chemical compound and disease context of SACCHARIN SODIUM

 

Biological context of SACCHARIN SODIUM

  • Subjects receiving this pairing greatly reduced their water intake in a retention test, in a similar manner to a group in which saccharin was paired with poisoning [20].
  • Both that saccharin and a highly purified extract of it increased the yield of sister chromatid exchanges in both types of cells [21].
  • The results, which were repeatable and statistically highly significant, indicated that the weak carcinogen, saccharin, is also mutagenic in the sense that it induces cytogenetic changes [21].
  • The saccharin clearance time technique was used to determine the effect upon nasal mucociliary transport of sine wave oscillations [22].
  • Retrospective epidemiology shows no evidence of such risk from saccharin at current levels of consumption [23].
 

Anatomical context of SACCHARIN SODIUM

 

Associations of SACCHARIN SODIUM with other chemical compounds

 

Gene context of SACCHARIN SODIUM

 

Analytical, diagnostic and therapeutic context of SACCHARIN SODIUM

  • Rats of line LC2-Hi that drank about 50 milliliters of a highly palatable saccharin solution daily for 28 consecutive days did not show morphine analgesia or an opioid form of stress-induced analgesia and were not responsive to naloxone [37].
  • Enhancement of oncogenesis in C3H/10T1/2 mouse embryo cell cultures by saccharin [24].
  • However, after treatment of the cells with a nontransforming initiating dose (0.1 microgram per milliliter) of 3-methylcholanthrene, continuous treatment with either sample of saccharin (100 micrograms per milliliter) led to significant transformation [24].
  • An epidemiologic study designed to elucidate the possible roles of the artificial sweeteners saccharin and cyclamate in human urinary bladder cancer was recently completed [38].
  • Female (Lewis x Brown Norway) F1 rats were conditioned by pairing consumption of a saccharin solution with an intraperitoneal injection of CY at 50 mg/kg of body weight 48 days before immunization [39].

References

  1. Relative risks of saccharin and calorie ingestion. Cohen, B.L. Science (1978) [Pubmed]
  2. Saccharin and other sweeteners: mutagenic properties. Batzinger, R.P., Ou, S.Y., Bueding, E. Science (1977) [Pubmed]
  3. Behaviorally conditioned immunosuppression and murine systemic lupus erythematosus. Ader, R., Cohen, N. Science (1982) [Pubmed]
  4. N-Methyl-N-nitrosourea and saccharin: effects on epithelium of normal human urinary bladder in vitro. El-Gerzawi, S., Heatfield, B.M., Trump, B.F. J. Natl. Cancer Inst. (1982) [Pubmed]
  5. Dose response of saccharin in induction of urinary bladder hyperplasias in Fischer 344 rats pretreated with N-butyl-N-(4-hydroxybutyl)nitrosamine. Nakanishi, K., Hagiwara, A., Shibata, M., Imaida, K., Tatematsu, M., Ito, N. J. Natl. Cancer Inst. (1980) [Pubmed]
  6. Case-control study of decaffeinated coffee consumption and pancreatic cancer. Wynder, E.L., Dieck, G.S., Hall, N.E. Cancer Res. (1986) [Pubmed]
  7. Genetics of behaviour: phenotypic and molecular study of rats derived from high- and low-alcohol consuming lines. Terenina-Rigaldie, E., Moisan, M.P., Colas, A., Beaugé, F., Shah, K.V., Jones, B.C., Mormède, P. Pharmacogenetics (2003) [Pubmed]
  8. Alcohol self-administration in two rat lines selectively bred for extremes in anxiety-related behavior. Henniger, M.S., Spanagel, R., Wigger, A., Landgraf, R., Hölter, S.M. Neuropsychopharmacology (2002) [Pubmed]
  9. Glucose-induced increase in memory performance in patients with schizophrenia. Newcomer, J.W., Craft, S., Fucetola, R., Moldin, S.O., Selke, G., Paras, L., Miller, R. Schizophrenia bulletin. (1999) [Pubmed]
  10. Effects of opiate agonists and antagonists on fluid intake and saccharin choice in the rat. Cooper, S.J. Neuropharmacology (1983) [Pubmed]
  11. Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac. Max, M., Shanker, Y.G., Huang, L., Rong, M., Liu, Z., Campagne, F., Weinstein, H., Damak, S., Margolskee, R.F. Nat. Genet. (2001) [Pubmed]
  12. Saccharin may act as a tumour promoter by inhibiting metabolic cooperation between cells. Trosko, J.E., Dawson, B., Yotti, L.P., Chang, C.C. Nature (1980) [Pubmed]
  13. Cell proliferation in carcinogenesis. Cohen, S.M., Ellwein, L.B. Science (1990) [Pubmed]
  14. Calcitonin: inhibitory effect on eating in rats. Freed, W.J., Perlow, M.J., Wyatt, R.J. Science (1979) [Pubmed]
  15. Genetic effects of impure and pure saccharin in yeast. Moore, C.W., Schmick, A. Science (1979) [Pubmed]
  16. Induction of morphological changes in the urothelium of cultured adult rat bladder by sodium saccharin and sodium cyclamate. Knowles, M.A., Jani, H., Hicks, R.M. Carcinogenesis (1986) [Pubmed]
  17. Effects of sugar on aggressive and inattentive behavior in children with attention deficit disorder with hyperactivity and normal children. Wender, E.H., Solanto, M.V. Pediatrics (1991) [Pubmed]
  18. Bicarbonate-based dental powder, fluoride, and saccharin inhibition of dental caries associated with Streptococcus mutans infection of rats. Tanzer, J.M., Grant, L., McMahon, T. J. Dent. Res. (1988) [Pubmed]
  19. Effect of dibutylnitrosamine and saccharin on glutamyl transpeptidase-positive foci and liver cancer. Pereira, M.A., Herren, S.L., Britt, A.L. Environ. Health Perspect. (1983) [Pubmed]
  20. Electrical stimulation of the amygdala as a conditioned stimulus in a bait-shyness paradigm. Phillips, A.G., LePiane, F.G. Science (1978) [Pubmed]
  21. Saccharin-induced sister chromatid exchanges in Chinese hamster and human cells. Wolff, S., Rodin, B. Science (1978) [Pubmed]
  22. High frequency oscillations improve nasal mucociliary transport. George, R.J., Moore-Gillon, V., Geddes, D.M. Lancet (1984) [Pubmed]
  23. The importance of synergy between weak carcinogens in the induction of bladder cancer in experimental animals and humans. Hicks, R.M., Chowaniec, J. Cancer Res. (1977) [Pubmed]
  24. Enhancement of oncogenesis in C3H/10T1/2 mouse embryo cell cultures by saccharin. Mondal, S., Brankow, D.W., Heidelberger, C. Science (1978) [Pubmed]
  25. Long-term feeding of sodium saccharin to nonhuman primates: implications for urinary tract cancer. Takayama, S., Sieber, S.M., Adamson, R.H., Thorgeirsson, U.P., Dalgard, D.W., Arnold, L.L., Cano, M., Eklund, S., Cohen, S.M. J. Natl. Cancer Inst. (1998) [Pubmed]
  26. Inhibition of iodinated nerve growth factor binding by the suspected tumor promoters saccharin and cyclamate. Ishii, D.N. J. Natl. Cancer Inst. (1982) [Pubmed]
  27. Suppression of ethanol-reinforced behavior by naltrexone is associated with attenuation of the ethanol-induced increase in dialysate dopamine levels in the nucleus accumbens. Gonzales, R.A., Weiss, F. J. Neurosci. (1998) [Pubmed]
  28. H-ras mutations in rat urinary bladder carcinomas induced by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide and sodium saccharin, sodium ascorbate, or related salts. Masui, T., Mann, A.M., Macatee, T.L., Okamura, T., Garland, E.M., Fujii, H., Pelling, J.C., Cohen, S.M. Cancer Res. (1991) [Pubmed]
  29. Distinction by concanavalin A agglutination between ulceration and repair of rat bladder epithelium induced by freezing or cyclophosphamide and the effect of sodium saccharin. Suzuki, T., Hasegawa, R., Murasaki, G., Cohen, S.M. Cancer Res. (1984) [Pubmed]
  30. Stimulation of DNA synthesis in calcium-deprived T51B liver cells by the tumor promoters phenobarbital, saccharin, and 12-O-tetradecanoylphorbol-13-acetate. Boynton, A.L., Whitfield, J.F. Cancer Res. (1980) [Pubmed]
  31. Inhibition by aspirin of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide initiation and sodium saccharin promotion of urinary bladder carcinogenesis in male F344 rats. Sakata, T., Hasegawa, R., Johansson, S.L., Zenser, T.V., Cohen, S.M. Cancer Res. (1986) [Pubmed]
  32. Design, synthesis, and in vitro inhibitory activity toward human leukocyte elastase, cathepsin G, and proteinase 3 of saccharin-derived sulfones and congeners. Groutas, W.C., Epp, J.B., Venkataraman, R., Kuang, R., Truong, T.M., McClenahan, J.J., Prakash, O. Bioorg. Med. Chem. (1996) [Pubmed]
  33. Polymorphisms in the taste receptor gene (Tas1r3) region are associated with saccharin preference in 30 mouse strains. Reed, D.R., Li, S., Li, X., Huang, L., Tordoff, M.G., Starling-Roney, R., Taniguchi, K., West, D.B., Ohmen, J.D., Beauchamp, G.K., Bachmanov, A.A. J. Neurosci. (2004) [Pubmed]
  34. Saccharin induces morphological changes and enhances prolactin production in GH4C1 cells. Brennessel, B.A., Keyes, K.J. In Vitro Cell. Dev. Biol. (1985) [Pubmed]
  35. Receptor crosstalk: characterization of mice deficient in dopamine D1 and adenosine A2A receptors. Short, J.L., Ledent, C., Drago, J., Lawrence, A.J. Neuropsychopharmacology (2006) [Pubmed]
  36. Specific alleles of bitter receptor genes influence human sensitivity to the bitterness of aloin and saccharin. Pronin, A.N., Xu, H., Tang, H., Zhang, L., Li, Q., Li, X. Curr. Biol. (2007) [Pubmed]
  37. Morphine tolerance in genetically selected rats induced by chronically elevated saccharin intake. Lieblich, I., Cohen, E., Ganchrow, J.R., Blass, E.M., Bergmann, F. Science (1983) [Pubmed]
  38. Saccharin, cyclamate, and human bladder cancer. No evidence of an association. Kessler, I.I., Clark, J.P. JAMA (1978) [Pubmed]
  39. Behaviorally conditioned suppression of a graft-versus-host response. Bovbjerg, D., Ader, R., Cohen, N. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
 
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