Lagopoulos L, Sunahara G I, Würzner H, Fliesen T, Stalder R
Nestec Ltd, Nestlé Research Centre, Lausanne, Switzerland.
Carcinogenesis. 1991 Feb;12(2):211-5. doi: 10.1093/carcin/12.2.211.
Caloric restriction depresses the development of several types of tumours, yet the mechanisms involved are poorly understood. In the present experiment we investigated the development of diethylnitrosamine (DEN)-induced liver tumours in mice treated with caffeine. The latter was found to reduce body growth, possibly due to increased energy expenditure, without reducing food consumption. Newborn mice received an i.p. injection of DEN. At weaning they were either fed lab chow ad libitum, with the same diet containing 0.2% (w/w) of caffeine, or their access to food was restricted to 70% of that consumed by the ad libitum group. Diet caloric restriction starting at weaning in male Swiss mice decreased the rate of development of glucose-6-phosphatase-deficient (G6Pd) preneoplastic foci. At the age of 24 weeks, 10% of the surface of a standardized liver section of ad libitum fed mice was G6Pase negative, compared to only 1% in the restricted mice due to a reduction of the number and size of these preneoplastic foci. The number and size of G6Pd foci decreased to the same extent with the ingestion of a lab chow supplemented with 0.2% of caffeine as with the diet restriction. This finding suggests that restriction slows down hepatic tumour growth by modifying body growth rather than by limited nutrient supply. In parallel, somatomedin-C (Sm-C) and insulin secretion following glucose challenge were decreased in diet restricted mice and those treated with 0.2% caffeine. The serum Sm-C and insulin levels were respectively 480 and 4.6 ng/ml in the restricted mice, 519 and 16.6 ng/ml in the caffeine-fed mice and 664 and 25.7 ng/ml in the ad libitum fed mice. Our results suggest that the decrease of secretion of these two hormones that are known mitogens for hepatocytes in vitro may be responsible at least in part for the reduction in the growth of liver tumours.
热量限制会抑制多种肿瘤的发展，但其涉及的机制仍知之甚少。在本实验中，我们研究了咖啡因处理的小鼠中由二乙基亚硝胺（DEN）诱导的肝肿瘤的发展情况。发现咖啡因会降低身体生长，这可能是由于能量消耗增加，而食物摄入量并未减少。新生小鼠腹腔注射DEN。断奶时，它们要么自由采食实验室饲料，要么采食含0.2%（w/w）咖啡因的相同饲料，要么食物摄入量限制在自由采食组的70%。雄性瑞士小鼠断奶后开始饮食热量限制，降低了葡萄糖-6-磷酸酶缺陷（G6Pd）癌前病灶的发展速度。在24周龄时，自由采食小鼠标准化肝脏切片表面的10%为G6Pase阴性，而限制采食小鼠中这一比例仅为1%，这是由于这些癌前病灶的数量和大小减少。摄入添加0.2%咖啡因的实验室饲料时，G6Pd病灶的数量和大小减少程度与饮食限制时相同。这一发现表明，限制通过改变身体生长而非有限的营养供应来减缓肝肿瘤的生长。同时，饮食限制小鼠和用0.2%咖啡因处理的小鼠在葡萄糖刺激后生长激素介质-C（Sm-C）和胰岛素分泌减少。限制采食小鼠的血清Sm-C和胰岛素水平分别为480和4.6 ng/ml，咖啡因喂养小鼠为519和16.6 ng/ml，自由采食小鼠为664和25.7 ng/ml。我们的结果表明，这两种在体外已知为肝细胞有丝分裂原的激素分泌减少可能至少部分导致了肝肿瘤生长的减少。
