Subchronic oral toxicity studies of Se-methylselenocysteine, an organoselenium compound for breast cancer prevention
Subchronic oral toxicity studies of Se-methylselenocysteine, an organoselenium compound for breast cancer prevention
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DOI：
10.1016/j.fct.2007.11.001
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发表时间：
2008-03-01
影响因子：
4.3
通讯作者：
McCormick, D. L.
中科院分区：
文献类型：
--
作者：
Johnson, W. D.;Morrissey, R. L.;McCormick, D. L.
硒-甲基硒代半胱氨酸（MSC）是一种有机硒化合物正在开发用于乳腺癌的化学预防。为了表征MSC毒性，CD大鼠接受0、0.5、1.0或2.0 mg/kg/天（0、3、6或12 mg/m2/天）的每日灌胃剂量，比格犬接受0、0.15、0.3或0.6 mg/kg/天（0、3、6或12 mg/m2/天）的每日灌胃剂量，持续28天。在大鼠中，MSC在两种性别中诱导剂量相关性肝肿大;仅在高剂量雌性中观察到轻度贫血、血小板减少和肝酶升高。显微镜病理学包括肝细胞变性（高剂量组雄性，所有剂量组雌性）;精子发生停滞（高剂量组雄性）;和黄体萎缩（中剂量组和高剂量组雌性）。在犬中，MSC在中剂量和高剂量雄性以及高剂量雌性中诱导轻度贫血。仅在肝脏中观察到犬的毒理学显著性显微镜病变（高剂量组雄性动物的紫癜和空泡变性，所有剂量组雄性动物的中区坏死）。基于所有剂量组雌性大鼠中观察到的肝脏病理学，大鼠中MSC的无明显不良作用水平（NOAEL）为
Se-methylselenocysteine (MSC) is an organoselenium compound being developed for breast cancer chemoprevention. To characterize MSC toxicity, CD rats received daily gavage doses of 0, 0.5, 1.0, or 2.0 mg/kg/day (0, 3, 6, or 12 mg/m(2)/day), and beagle dogs received daily gavage doses of 0, 0.15, 0.3, or 0.6 mg/kg/day (0, 3, 6, or 12 mg/m(2)/day) for 28 days. In rats, MSC induced dose-related hepatomegaly in both sexes; mild anemia, thrombocytopenia, and elevated liver enzymes were observed in high dose females only. Microscopic pathology included hepatocellular degeneration (high dose males, all doses in females); arrested spermatogenesis (high dose males); and atrophy of corpora lutea (middle and high dose females). In dogs, MSC induced mild anemia in middle and high dose males, and in high dose females. Toxicologically significant microscopic lesions in dogs were seen only in the liver (peliosis and vacuolar degeneration in high dose males, midzonal necrosis in males in all dose groups). Based on liver pathology seen in female rats in all dose groups, the no observed adverse effect level (NOAEL) for MSC in rats is