Hu Ying, McIntosh Graeme H, Le Leu Richard K, Woodman Richard, Young Graeme P
Department of Medicine, Flinders Cancer Control Alliance, Flinders University of South Australia, Adelaide, Australia.
Cancer Res. 2008 Jun 15;68(12):4936-44. doi: 10.1158/0008-5472.CAN-07-6042.
The chemical form and bioavailability of dietary selenium may influence its protectiveness against colorectal cancer. Selenium is readily incorporated into milk proteins by feeding cows with selenized-yeast. This study examined whether a dairy source of organic selenium (as milk proteins) is more effective than a yeast source at inhibiting oncogenesis in carcinogen-treated mice and whether it regulates the homeostatic response to carcinogen-induced DNA damage. Dietary interventions are as follows: selenium-enriched milk protein isolate (Tatura-Bio Se; 0.5 or 1 ppm selenium) or milk protein control and selenized-yeast (Sel-Plex; 1 or 4 ppm selenium) with casein or casein alone as control. After 4 weeks on diet, mice received a single azoxymethane (10 mg/kg) injection to induce mutations and were killed 6 hours later. Measures were as follows: plasma selenium, cell proliferation, and acute apoptotic response to azoxymethane (AARGC). Separate groups of mice on the same diets were given 4 weekly azoxymethane (15 mg/kg) injections to induce oncogenesis. Mice were killed 6 or 30 weeks after the last azoxymethane injection. Measures were as follows: aberrant crypt foci (ACF), cancers, and K-ras mutations. Dairy-selenium at 1 ppm significantly suppressed ACF and cancers, whereas yeast-selenium at an equivalent selenium intake had no effect. Dairy-selenium significantly increased plasma selenium levels and AARGC, and reduced cell proliferation and frequency of K-ras mutations in ACF relative to an equivalent dose of selenium from yeast. Selenium-enriched milk protein isolate is superior to selenized-yeast in terms of its bioavailability and capacity to suppress oncogenesis. Suppression may be a consequence of enhanced apoptotic deletion of azoxymethane-induced DNA lesions and the subsequent reduction in frequency of K-ras mutations.
膳食硒的化学形态和生物利用度可能会影响其对结直肠癌的预防作用。通过给奶牛喂食硒化酵母，硒很容易被整合到乳蛋白中。本研究调查了有机硒的乳制品来源（作为乳蛋白）在抑制致癌物处理小鼠的肿瘤发生方面是否比酵母来源更有效，以及它是否调节对致癌物诱导的DNA损伤的稳态反应。膳食干预如下：富含硒的乳蛋白分离物（塔图拉生物硒；0.5或1 ppm硒）或乳蛋白对照以及硒化酵母（Sel-Plex；1或4 ppm硒），以酪蛋白或单独的酪蛋白作为对照。饮食4周后，小鼠接受单次注射氧化偶氮甲烷（10 mg/kg）以诱导突变，并在6小时后处死。检测指标如下：血浆硒、细胞增殖以及对氧化偶氮甲烷的急性凋亡反应（AARGC）。将相同饮食的另一组小鼠每周注射4次氧化偶氮甲烷（15 mg/kg）以诱导肿瘤发生。在最后一次注射氧化偶氮甲烷后6周或30周处死小鼠。检测指标如下：异常隐窝灶（ACF）、癌症以及K-ras突变。1 ppm的乳制品硒显著抑制了ACF和癌症，而等量硒摄入的酵母硒则没有效果。与等量的酵母硒相比，乳制品硒显著提高了血浆硒水平和AARGC，并降低了ACF中的细胞增殖和K-ras突变频率。富含硒的乳蛋白分离物在生物利用度和抑制肿瘤发生的能力方面优于硒化酵母。抑制作用可能是氧化偶氮甲烷诱导的DNA损伤的凋亡清除增强以及随后K-ras突变频率降低的结果。
