Rodríguez-Burford Cristina, Steele Vernon E, Anderson Amy S, Stockard Cecil R, Weiss Heidi L, Eto Isao, Johanning Gary L, Grizzle William E, Grubbs Clinton J
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Nutr Cancer. 2002;43(1):67-75. doi: 10.1207/S15327914NC431_8.
Moderate reductions (< or = 15%) in body weight gain, similar to those observed after administration of some chemopreventive agents in chemically induced mammary cancer models, will result in decreased mammary cancers (up to 55%). The objective of this study was to determine whether changes in mammary gland differentiation, proliferation, apoptosis, and estradiol and progesterone levels are affected by moderate reductions in body weight induced after chemopreventive agent treatment and dietary restriction. The body weights of female Sprague-Dawley rats were reduced by dietary restrictions to match those of rats receiving 4-hydroxyphenylretinamide (4-HPR) at a dose known to inhibit methylnitrosourea (MNU)-induced mammary cancers. 4-HPR supplementation or dietary restrictions began 1 wk before MNU administration at 50 days of age. Mammary gland differentiation, proliferation, apoptosis, and serum levels of estradiol and progesterone were measured at 50, 57, and 71 days of age. Casein expression, proliferating cellular nuclear antigen expression, and apoptosis were not significantly different from controls in the dietary-restricted group. Proliferating cellular nuclear antigen expression was significantly lower in 4-HPR-treated animals than in controls at 57 days of age. The diameter of the mammary gland ducts was smaller at 71 days of age in the treatment groups. A decrease in estradiol levels for each group was observed at 50 days of age, but not at later time points. Progesterone levels were reduced in the 4-HPR group, but not in the dietary-restricted group, during each time period. It would appear that the observed decrease in mammary cancers observed with moderate reductions in body weight gain might be due to multiple related factors different from those related to 4-HPR treatment.
体重增加适度降低（≤15%），类似于在化学诱导的乳腺癌模型中给予某些化学预防剂后观察到的情况，将导致乳腺癌发病率降低（高达55%）。本研究的目的是确定在化学预防剂治疗和饮食限制后诱导的体重适度降低是否会影响乳腺分化、增殖、凋亡以及雌二醇和孕酮水平。通过饮食限制降低雌性Sprague-Dawley大鼠的体重，使其与接受已知可抑制甲基亚硝基脲（MNU）诱导的乳腺癌剂量的4-羟基苯基维甲酸（4-HPR）的大鼠体重相匹配。在50日龄MNU给药前1周开始补充4-HPR或进行饮食限制。在50、57和71日龄时测量乳腺分化、增殖、凋亡以及雌二醇和孕酮的血清水平。饮食限制组的酪蛋白表达、增殖细胞核抗原表达和凋亡与对照组无显著差异。在57日龄时，4-HPR处理的动物中增殖细胞核抗原表达显著低于对照组。在71日龄时，治疗组的乳腺导管直径较小。在50日龄时观察到每组雌二醇水平均下降，但在随后的时间点未观察到。在每个时间段，4-HPR组的孕酮水平降低，但饮食限制组未降低。体重增加适度降低时观察到的乳腺癌发病率下降似乎可能是由于多种相关因素，与4-HPR治疗相关的因素不同。
