Evaluation of organoselenium compounds for potential chemopreventive properties in colon carcinogenesis.
As a part of a program aimed to develop less toxic and more effective chemopreventive organoselenium compounds than inorganic selenium, we have evaluated benzyl selenocyanate (BSC) and its o-, m-, p-nitro and -methoxy isomers, o-, m-, and p-isomers of phenylenebis(methylene)selenocyanate (XSC), dibenzyl diselenide (DDS), and 2,2'-diselenobis[((N,N-dimethylamino)methyl)- benzene]bis(hydrochloride salt) (DSBDB) for their potential colon tumor inhibitory properties using azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF), a preneoplastic lesion, in male F344 rats prior to preclinical efficacy study. In the first experiment, the effect of these agents administered during initiation and postinitiation periods of carcinogenesis was investigated. Male F344 rats were fed diets containing 8 ppm Na2SeO3 or 10 ppm of each BSC and its analogues, DDS and DSBDB or 20 ppm of each XSC analogue, two weeks prior to AOM (15 mg/kg body wt., once weekly for two weeks, s.c.) administration and during and until 8 weeks after AOM treatment. Formalin-fixed and methylene blue stained colons were scored for AOM-induced ACF using the light microscope. Taking body weight gains and multiplicity of 4 or more AC/focus, the inhibitory effects of Na2SeO3, o-, m- and p-methoxy-BSC, p-XSC and DDS were much greater than those of the other selenium compounds. In the second study, the effects of these agents when administered during the initiation or postinitiation periods were investigated. The results indicated that o-, m-, and p-methoxy-BSC, DDS and p-XSC significantly inhibited crypt multiplicity during the initiation period whereas o-, and p-methoxy-BSC, p-XSC and DDS suppressed crypt multiplicity during the postinitiation period. It is concluded that o-, and p-methoxy-BSC, p-XSC and DDS possess potential chemopreventive properties in colon cancer. Further studies are warranted to evaluated these agents for chemopreventive properties in preclinical efficacy studies.
Reddy
B S
BS
Division of Nutritional Carcinogenesis, American Health Foundation, Valhalla, New York 10595.
Upadhyaya
P
P
Simi
B
B
Rao
C V
CV
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001397:Azoxymethane; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D004032:Diet; D008297:Male; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D018038:Sodium Selenite / Q000008:administration & dosage / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors; D015430:Weight Gain
D016588:Anticarcinogenic Agents; D016566:Organoselenium Compounds; D018038:Sodium Selenite; D001397:Azoxymethane