Zhu Z, Jiang W, Thompson H J
Center for Nutrition in the Prevention of Disease, AMC Cancer Research Center, Lakewood, CO 80214, USA.
Carcinogenesis. 1999 Sep;20(9):1721-6. doi: 10.1093/carcin/20.9.1721.
Energy restriction (ER) has documented beneficial effects on numerous diseases including cancer, yet the mechanism(s) that accounts for these effects is unknown. Experiments were designed to determine the effect of ER: (i) on the growth and development of the mammary gland; (ii) on the growth of carcinomas induced in the mammary gland by treatment with 1-methyl-1-nitrosourea (MNU); (iii) on rates of cell proliferation and apoptosis in pre-malignant and malignant mammary lesions. Mammary carcinogenesis was induced in female Sprague-Dawley rats by the i.p. administration of MNU (50 mg MNU/kg body wt) at 21 days of age. Rats were randomized to one of four dietary treatment groups: ad libitum fed or restriction of calorie intake to 90, 80 or 60% of ad libitum intake. ER reduced the ductal extension of the mammary gland into the fat pad in proportion to its effect on growth measured as body weight, however, the reduction in ductal branching, breast density and carcinoma volume by ER was greater than its effect on body weight. An animal's breast density was predictive of its carcinogenic response, irrespective of the level of ER imposed. While ER inhibited cell proliferation and induced apoptosis in pre-malignant and malignant mammary gland lesions, the magnitude of these effects make it unlikely that they fully account for the protective effects of ER against mammary carcinogenesis.
能量限制（ER）已被证明对包括癌症在内的多种疾病具有有益作用，但其产生这些作用的机制尚不清楚。本实验旨在确定能量限制的影响：（i）对乳腺生长发育的影响；（ii）对用1-甲基-1-亚硝基脲（MNU）处理诱导的乳腺肿瘤生长的影响；（iii）对癌前和恶性乳腺病变中细胞增殖和凋亡率的影响。在21日龄时，通过腹腔注射MNU（50 mg MNU/kg体重）诱导雌性Sprague-Dawley大鼠发生乳腺癌变。将大鼠随机分为四个饮食处理组之一：自由采食组或将热量摄入限制为自由摄入量的90%、80%或60%。能量限制按其对以体重衡量的生长的影响比例，减少了乳腺导管向脂肪垫的延伸，然而，能量限制对导管分支、乳腺密度和癌体积的降低作用大于其对体重的影响。无论施加何种能量限制水平，动物的乳腺密度都可预测其致癌反应。虽然能量限制抑制了癌前和恶性乳腺病变中的细胞增殖并诱导了细胞凋亡，但这些作用的程度表明它们不太可能完全解释能量限制对乳腺癌变的保护作用。
