Evaluation of organoselenium compounds for potential chemopreventive properties in colon cancer.
Our previous studies have demonstrated that dietary benzylselenocyanate (BSC) and 1,4-phenylenebis (methylene) selenocyanate (p-XSC); organoselenium compounds, act as potential chemopreventive agents in colon carcinogenesis in F344 rats. As a part of a program aimed to develop less toxic and more effective chemopreventive organoselenium compounds than inorganic selenium and BSC, we evaluated the positional isomers of BSC namely o-, m-, and p-methoxy BSC and dibenzyl diselenide (DDS) for their potential chemopreventive properties using colonic epithelial cell proliferation as an efficacy endpoint. p-XSC and inorganic selenium, which were found to inhibit colon carcinogenesis in earlier preclinical efficacy study, were included as positive controls. Male F344 rats were fed the control diet containing 8 ppm Na2SeO3 or 10 ppm of each o-, m-, and p-methoxy BSC and DDS equivalent to 4.1 ppm Se or 20 ppm p-XSC (10 ppm Se) 2 weeks prior to carcinogen (AOM, 15 mg/kg body wt., once weekly for 2 weeks) administration and during and until 8 weeks after AOM treatment. Vehicle-control animals received an equal volume of normal saline. One hour prior to sacrifice, all animals were injected with bromodeoxyuridine (BrdU, 20 mg/kg body wt.). Administration of o-, m-, and p-methoxy BSC, p-XSC, DDS, and Na2SeO3 resulted in decreased colonic labeling index in animal treated with AOM compared to control diet. Notably, p-XSC and Na2SeO3, which showed previously colon tumor inhibitory activity in preclinical efficacy study, were also effective in the present study. The results of our previous and current studies indicate that structurally modified synthetic organoselenium compounds may have great potential as chemopreventive agents.
Reddy
B S
BS
Division of Nutritional Carcinogenesis, American Health Foundation, Valhalla, NY 10595, USA.
Wynn
T T
TT
el-Bayoumy
K
K
Upadhyaya
P
P
Fiala
E
E
Rao
C V
CV
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001397:Azoxymethane; D001593:Benzyl Compounds / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000166:cytology / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D003485:Cyanates / Q000627:therapeutic use; D007536:Isomerism; D008297:Male; D016566:Organoselenium Compounds / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344
D016588:Anticarcinogenic Agents; D001593:Benzyl Compounds; D002273:Carcinogens; D003485:Cyanates; D016566:Organoselenium Compounds; C073177:dibenzyl diselenide; C054108:benzyl selenocyanate; C074153:1,4-phenylenebis(methylene)selenocyanate; D001397:Azoxymethane