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 h ave evaluated benzyl selenocyanate (BSC) and its o-, m-, p-nitro and - methoxy isomers, o-, m-, and p-isomers of phenylenebis(methylene)selen ocyanate (XSC), dibenzyl diselenide (DDS), and N,N-dimethylamino)methy l}-benzene]bis(hydrchloride salt) (DSBDB) for their potential colon tu mor inhibitory properties using azoxymethane (AOM)-induced colonic abe rrant crypt foci (ACF), a preneoplastic lesion, in male F344 rats prio r to preclinical efficacy study. In the first experiment, the effect o f these agents administered during initiation and postinitiation perio ds of carcinogenesis was investigated Male F344 rats were fed diets co ntaining 8 ppm Na2SeO3 or 10 ppm of each BSC and its analogues, DDS an d 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 durin g and until 8 weeks after AOM treatment. Formalin-fixed and methylene blue stained colons were scored for A OM-induced A CF rising 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 compou nds. In the second study, the effects of these agents when administere d during the initiation or postinitiation periods were investigated. T he results indicated that o-, mi and p-methoxy-BSC, DDS and p-XSC sign ificantly inhibited crypt multiplicity during the initiation period wh ereas o-, and p-methoxy-BSC, p-XSC and DDS suppressed crypt multiplici ty during the postinitiation period. It is concluded that o-, and p-me thoxy-BSC, p-XSC and DDS possess potential chemopreventive properties in colon cancer. Further studies are warranted to evaluated these agen ts for chemopreventive properties in preclinical efficacy studies.