Rodríguez-Burford C, Lubet R A, Eto I, Juliana M M, Kelloff G J, Grubbs C J, Steele V E
Chemoprevention Center, University of Alabama at Birmingham, 35294, USA.
Carcinogenesis. 1999 Jan;20(1):71-6. doi: 10.1093/carcin/20.1.71.
These studies examined whether the small to moderate reductions in body weight gain (< or = 15%) affect mammary carcinogenesis. Beginning 1 week prior to methylnitrosourea (MNU) administration (experiment 1), rats received diets supplemented with 4-hydroxyphenylretinamide (4-HPR) (782 mg/kg of diet) and retinyl acetate (328 mg/kg of diet) or underwent food restrictions. Rats were administered an i.v. dose of MNU (50 mg/kg body wt) at 50 days of age. Although the final body weights were similarly depressed by 4-HPR (8%) and by retinyl acetate (11%) from rats fed ad libitum, the kinetics of inhibition were quite different. Whereas 4-HPR caused an acute decrease in body weight at the time it was administered, the effect of retinyl acetate was more chronic. At 110 days after the administration of MNU, the average number of mammary cancers per rat was 4.9 for rats fed ad libitum, 1.3 for rats fed 4-HPR, 3.1 when body weights were matched to 4-HPR-treated rats, 1.9 for retinyl acetate and 3.2 when body weights were matched to retinyl acetate. Experiment II was performed to determine the minimal degree of acute body weight gain reduction that would alter MNU-induced mammary carcinogenesis. Body weight gain depressions of 3, 6, 9, 12 and 15% were initiated at 43 days of age by dietary restrictions and MNU was administered at 50 days of age. At 120 days after MNU, the percentage decreases in mammary cancer multiplicity in the various groups were 14, 15, 41, 44 and 55%, respectively. These data demonstrate that moderate reductions (9-15%) in body weight gain, in particular when occurring during the initiation and early promotion stages can greatly affect cancer multiplicity.
这些研究考察了体重增加的小幅至中度降低（≤15%）是否会影响乳腺癌发生。在给予甲基亚硝基脲（MNU）前1周开始（实验1），大鼠接受补充了4-羟基苯维甲酸（4-HPR）（782毫克/千克饲料）和醋酸视黄酯（328毫克/千克饲料）的饮食，或进行食物限制。大鼠在50日龄时静脉注射MNU（50毫克/千克体重）。尽管与随意进食的大鼠相比，4-HPR（8%）和醋酸视黄酯（11%）同样使最终体重降低，但抑制的动力学有很大不同。4-HPR在给药时导致体重急性下降，而醋酸视黄酯的作用更具慢性。在给予MNU后110天，随意进食的大鼠每只平均乳腺癌数量为4.9个，喂食4-HPR的大鼠为1.3个，体重与4-HPR处理组大鼠匹配时为3.1个，醋酸视黄酯组为1.9个，体重与醋酸视黄酯组大鼠匹配时为3.2个。进行实验II以确定能改变MNU诱导的乳腺癌发生的急性体重增加降低的最小程度。在43日龄时通过饮食限制使体重增加降低3%、6%、9%、12%和15%，并在50日龄时给予MNU。在给予MNU后120天，各实验组乳腺癌多发性降低的百分比分别为14%、15%、41%、44%和55%。这些数据表明，体重增加的中度降低（9%-15%），尤其是在启动期和早期促进期发生时，会极大地影响癌症多发性。
