© 1997 by Oxford University Press
Journal Of The National Cancer Institute, Vol 89, 506-512, Copyright © 1997 by Oxford University Press
BS Reddy, A Rivenson, K El-Bayoumy, P Upadhyaya, B Pittman and CV Rao
BACKGROUND: Observational and experimental studies have suggested that
dietary supplementation with selenium can inhibit the development of colon
cancer. However, many forms of selenium are toxic. Consequently, the
development of efficacious compounds with low toxicity has been pursued.
PURPOSE: Two synthetic organoselenium compounds, p-methoxy- benzyl
selenocyanate (p-methoxy-BSC) and 1,4- phenylenebis(methylene)selenocyanate
(p-XSC), were tested for their ability to inhibit colon carcinogenesis in
rats that were treated with the carcinogen azoxymethane and fed low- or
high-fat diets. METHODS: Groups of 5-week-old male F344 rats (42 animals/
group) were fed either a high-fat diet or a low-fat diet with or without
added p-methoxy-BSC (10 or 20 parts per million [ppm]) or p-XSC (20 ppm).
Two weeks later, 30 animals in each group received a subcutaneous injection
of azoxymethane (15 mg/kg body weight); 1 week later, they received a
second injection. The remaining 12 rats in each group received two
injections of saline. Three days after the second injection of carcinogen
or saline, animals being fed diets with p-methoxy-BSC or p- XSC were
switched to corresponding organoselenium-free low- or high-fat diets for
the remainder of the study to determine the effects of the selenium
compounds on the initiation phase of colon carcinogenesis. At that time,
groups of animals that had been maintained on organoselenium- free low- or
high-fat diets were switched to diets containing p-methoxy- BSC or p-XSC
until the end of the study to determine the effects of these compounds on
the postinitiation phase of colon carcinogenesis. All animals were killed
during the 38th week after azoxymethane or saline treatment, and
histopathologic analysis of the colon tumors was performed. Colon tumor
incidence and multiplicity were analyzed statistically. RESULTS: No obvious
toxic effects were observed following dietary administration of 10 or 20
ppmp-methoxy-BSC or 20 ppm p-XSC. Administration of 20 ppm p-methoxy-BSC in
a high-fat diet during the initiation and postinitiation phases of colon
carcinogenesis significantly (statistically) reduced colon tumor incidence;
10 ppmp- methoxy-BSC in a high-fat diet significantly reduced colon tumor
incidence but only when it was given during the postinitiation phase. Colon
tumor incidence was also significantly reduced when 20 ppm p-XSC was given
in a high-fat diet during the initiation phase of colon carcinogenesis.
When 20 ppm p-XSC was administered in either a high-fat diet or a low-fat
diet during the postinitiation phase, both colon tumor incidence and
multiplicity were significantly reduced; the greatest reductions were in
animals fed a low-fat diet. CONCLUSIONS: In this model system,
p-methoxy-BSC and p-XSC are effective agents for the chemoprevention of
colon cancer. The effects of p-XSC were enhanced in animals fed a low-fat
diet.
ARTICLES
Chemoprevention of colon cancer by organoselenium compounds and impact of high- or low-fat diets
Division of Nutritional Carcinogenesis, American Health Foundation, Valhalla, NY 10595, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. A. Narayanan, N. K. Narayanan, D. Desai, B. Pittman, and B. S. Reddy Effects of a combination of docosahexaenoic acid and 1,4-phenylene bis(methylene) selenocyanate on cyclooxygenase 2, inducible nitric oxide synthase and {beta}-catenin pathways in colon cancer cells Carcinogenesis, December 1, 2004; 25(12): 2443 - 2449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K. Wali, D. Stoiber, L. Nguyen, J. Hart, M. D. Sitrin, T. Brasitus, and M. Bissonnette Ursodeoxycholic Acid Inhibits the Initiation and Postinitiation Phases of Azoxymethane-induced Colonic Tumor Development Cancer Epidemiol. Biomarkers Prev., November 1, 2002; 11(11): 1316 - 1321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. V. Rao, C-Q. Wang, B. Simi, J. G. Rodriguez, I. Cooma, K. El-Bayoumy, and B. S. Reddy Chemoprevention of Colon Cancer by a Glutathione Conjugate of 1,4-Phenylenebis(methylene)selenocyanate, a Novel Organoselenium Compound with Low Toxicity Cancer Res., May 1, 2001; 61(9): 3647 - 3652. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. W. Finley, C. D. Davis, and Y. Feng Selenium from High Selenium Broccoli Protects Rats from Colon Cancer J. Nutr., September 1, 2000; 130(9): 2384 - 2389. [Abstract] [Full Text]
|
|
|
|
|
|
C. V. Rao, I. Cooma, J. G.R. Rodriguez, B. Simi, K. El-Bayoumy, and B. S. Reddy Chemoprevention of familial adenomatous polyposis development in the APCmin mouse model by 1,4-phenylene bis(methylene)selenocyanate Carcinogenesis, April 1, 2000; 21(4): 617 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. Reddy Novel Approaches to the Prevention of Colon Cancer by Nutritional Manipulation and Chemoprevention Cancer Epidemiol. Biomarkers Prev., March 1, 2000; 9(3): 239 - 247. [Abstract] [Full Text]
|
|
|
|
 |
|
 M LANGMAN and P BOYLE Chemoprevention of colorectal cancer Gut, October 1, 1998; 43(4): 578 - 585. [Abstract] [Full Text] [PDF]
|
|