Structure-activity relationships among the ortho-, meta- and para-isomers of phenylenebis (methylene)seleno cyanate (XSC) as inhibitors of 7,12-dimethylbenz(a)anthracene-DNA binding in mammary glands of female CD rats

  • Authors:
    • Y Chae
    • P Upadhyaya
    • K ElBayoumy
  • View Affiliations

  • Published online on: Monday, September 1, 1997
  • Pages: 1067-1071
  • DOI: 10.3892/or.4.5.1067

Abstract

As shown earlier p-XSC inhibits DMBA-induced mammary cancer in female CD rats. This inhibition is due, in part, to inhibition of DMBA-DNA adduct formation in the target organ. We have now utilized the DMBA-DNA binding assay to evaluate the chemopreventive potential of positional isomers of XSC (o-, m- and p-XSC) applied at selenium doses of 5 and 15 ppm; p-XTC, the sulfur analog of p-XSC, was used at an equimolar dose to determine whether selenium is required for the observed inhibitory effect. Selenium and sulfur compounds were administered in a semipurified high-fat diet (23.5% corn oil). Rats were fed for 1 week prior to oral administration of a single dose of [H-3]DMBA (5 mg/rat); animals were sacrificed 24 h later, DNA was isolated from mammary fat pads and levels of total binding were determined. All agents produced a dose-dependent inhibition of DMBA-DNA binding in the mammary tissues. The inhibition at 5, respectively 15 ppm Se in the form of XSC isomers and at 30 mu M, respectively 90 mu M in the form of p-XTC was: o-XSC (27%, 42%); m-XSC (32%, 47%); p-XSC (22%, 29%); and p-XTC (10%, 20%); only inhibition by dietary o-XSC and m-XSC at 15 ppm Se reached statistical significance (p<0.05). Thus, o-XSC and m-XSC equally inhibit DMBA-DNA binding and both are better inhibitors than p-XSC; the latter appears to be slightly more effective than its sulfur analog p-XTC. Clearly, the structure of the selenium-containing compound is a critical factor in determining the extent of inhibition of DMBA-DNA binding. The described short-term in vivo assay may constitute the basis for future selection of chemopreventive agents in the rat mammary tumor model system.
Journal Cover

September 1997
Volume 4 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

2013 Impact Factor: 2.191
Ranked #33/202 Oncology
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APA
Chae, Y., Upadhyaya, P., & ElBayoumy, K. (1997). Structure-activity relationships among the ortho-, meta- and para-isomers of phenylenebis (methylene)seleno cyanate (XSC) as inhibitors of 7,12-dimethylbenz(a)anthracene-DNA binding in mammary glands of female CD rats. Oncology Reports, 4(5), 1067-1071.
MLA
Chae, Upadhyaya, and K ElBayoumy. "Structure-activity relationships among the ortho-, meta- and para-isomers of phenylenebis (methylene)seleno cyanate (XSC) as inhibitors of 7,12-dimethylbenz(a)anthracene-DNA binding in mammary glands of female CD rats." Oncology Reports Oncology Reports 4.5 (1997): 1067-1071.
Chicago
Chae, Upadhyaya, and K ElBayoumy. "Structure-activity relationships among the ortho-, meta- and para-isomers of phenylenebis (methylene)seleno cyanate (XSC) as inhibitors of 7,12-dimethylbenz(a)anthracene-DNA binding in mammary glands of female CD rats." Oncology Reports Oncology Reports 4 no. 5 (1997): 1067-1071.