Reddy B S, Upadhyaya P, Simi B, Rao C V
Division of Nutritional Carcinogenesis, American Health Foundation, Valhalla, New York 10595.
Anticancer Res. 1994 Nov-Dec;14(6B):2509-14.
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.
作为旨在开发比无机硒毒性更低、更有效的化学预防有机硒化合物项目的一部分，在临床前疗效研究之前，我们使用雄性F344大鼠中由氧化偶氮甲烷（AOM）诱导的结肠异常隐窝病灶（ACF，一种癌前病变），评估了苄基硒氰酸盐（BSC）及其邻、间、对硝基和甲氧基异构体、亚苯基双（亚甲基）硒氰酸盐（XSC）的邻、间和对异构体、二苄基二硒化物（DDS）以及2,2'-二硒双[（（N,N-二甲基氨基）甲基）苯]双（盐酸盐）（DSBDB）的潜在结肠肿瘤抑制特性。在第一个实验中，研究了这些试剂在致癌起始期和起始后期给药的效果。在给予AOM（15 mg/kg体重，每周一次，共两周，皮下注射）前两周以及AOM治疗期间和之后直至8周，雄性F344大鼠喂食含有8 ppm亚硒酸钠或10 ppm每种BSC及其类似物、DDS和DSBDB或20 ppm每种XSC类似物的饲料。使用光学显微镜对用福尔马林固定并经亚甲蓝染色的结肠进行AOM诱导的ACF评分。考虑体重增加以及每个病灶4个或更多AC的数量，亚硒酸钠、邻、间和对甲氧基-BSC、对-XSC和DDS的抑制作用远大于其他硒化合物。在第二项研究中，研究了这些试剂在起始期或起始后期给药时的效果。结果表明，邻、间和对甲氧基-BSC、DDS和对-XSC在起始期显著抑制隐窝数量，而邻和对甲氧基-BSC、对-XSC和DDS在起始后期抑制隐窝数量。结论是，邻和对甲氧基-BSC、对-XSC和DDS在结肠癌中具有潜在的化学预防特性。有必要在临床前疗效研究中进一步评估这些试剂的化学预防特性。
