Jacobs M M
Cancer Res. 1983 Apr;43(4):1646-9.
The inhibitory effect of selenium (Na2SeO3) on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in male Sprague-Dawley rats is presented. A 4-ppm selenium supplement to the drinking water was provided concurrently with DMH treatment and continued until death or sacrifice. Rats were administered 10 weekly injections of 10 mg DMH per kg body weight. Thirtyone weeks following the tenth DMH injection, all surviving animals were sacrificed. At sacrifice, the colon tumor incidence in DMH-only controls was 8 of 28 (29%). Selenium supplementation significantly (p less than 0.01) reduced the colon tumor incidence to 1 of 37 (3%). The cumulative colon tumor incidence for all animals found dead or sacrificed was also significantly (p less than 0.05) reduced from 11 of 40 in DMH controls to 3 of 40 in DMH-selenium-supplemented rats. The total number of colon tumors was reduced from 13 to 3, and the average number of tumors per rat from 1.2 to 1.0 by supplemental selenium. The majority (greater than 65%) of all tumors were located in the distal colon. The serum glutamic oxaloacetic transaminase, alkaline phosphatase, and complete blood count were normal and equivalent for the DMH only, DMH-selenium, and untreated control groups in this study. The glutathione S-transferase activity in liver cytosol preparations was increased from 39.6 +/- 7.3 (S.D.) microM product/min/mg (DMH only) to 67.6 +/- 5.8 microM product/min/mg by selenium only and to 54.3 +/- 10.6 microM product/min/mg in selenium-DMH-treated rats. Protection by selenium may in part be attributed to enhanced detoxification of carcinogenic electrophiles.
本文介绍了硒（亚硒酸钠）对雄性斯普拉格-道利大鼠中1,2-二甲基肼（DMH）诱导的结肠癌发生的抑制作用。在DMH处理的同时，给饮用水中添加4 ppm的硒，并持续至动物死亡或处死后。给大鼠每周注射10次，每次每千克体重注射10 mg DMH。在第十次注射DMH后31周，处死所有存活的动物。处死时，仅接受DMH处理的对照组中结肠肿瘤发生率为28只中有8只（29%）。补充硒显著（p<0.01）降低结肠肿瘤发生率至37只中有1只（3%）。所有死亡或被处死动物的累积结肠肿瘤发生率也显著（p<0.05）降低，从DMH对照组的40只中有11只降至补充硒的DMH处理大鼠的40只中有3只。补充硒使结肠肿瘤总数从13个减少到3个，每只大鼠的平均肿瘤数从1.2个减少到1.0个。所有肿瘤的大多数（>65%）位于结肠远端。在本研究中，仅接受DMH处理、接受DMH-硒处理和未处理的对照组的血清谷草转氨酶、碱性磷酸酶和全血细胞计数均正常且相当。肝胞质溶胶制剂中的谷胱甘肽S-转移酶活性从仅接受DMH处理时的39.6±7.3（标准差）微摩尔产物/分钟/毫克增加到仅补充硒时的67.6±5.8微摩尔产物/分钟/毫克，并在接受硒-DMH处理的大鼠中增加到54.3±10.6微摩尔产物/分钟/毫克。硒的保护作用可能部分归因于致癌亲电试剂解毒作用的增强。
