Aylsworth C F, Van Vugt D A, Sylvester P W, Meites J
Cancer Res. 1984 Jul;44(7):2835-40.
The role of estrogen and prolactin in high-fat (HF) dietary stimulation of carcinogen-induced mammary tumors was examined in female Sprague-Dawley rats. At 55 days of age, the rats were given injections i.v. of 5 mg of dimethylbenz(a)anthracene and, 5 days later, rats were sham- or bilaterally ovariectomized. Ten days after dimethylbenz(a)anthracene administration, the rats were placed on either a 20.0% HF diet or a 4.5% control fat (CF) diet and were then subjected to various drug and endocrine treatments to maintain uniform levels of circulating estrogen and prolactin. Sham-operated intact rats and bilaterally ovariectomized rats were given daily injections of haloperidol to increase prolactin secretion, bromocryptine to decrease prolactin secretion, and/or estradiol benzoate (EB). The intact rats fed the HF diet showed significant stimulation of all parameters of mammary tumor development when compared to similarly treated rats fed the CF diet. In ovariectomized rats fed either the HF or CF diet, there was nearly complete inhibition of mammary tumor development. When the HF diet was given to ovariectomized rats treated daily with either haloperidol or EB, or EB and bromocryptine, some parameters of mammary tumor development were enhanced by the HF diet. However, in all cases, mammary tumorigenesis was reduced when compared to sham-operated control rats. Ovariectomized rats fed the HF diet and given both EB and haloperidol exhibited significantly greater tumor number per rat, increased average tumor size, and reduced tumor latency period when compared to similarly treated rats fed the CF diet. However, these parameters of mammary tumorigenesis were still reduced when compared to those of sham-control rats fed the HF diet. These results indicate that a HF diet requires adequate circulating levels of estrogen and prolactin to maximally promote increased mammary tumorigenesis in dimethylbenz(a)anthracene-treated rats. Moreover, the enhancing effects of a HF diet on mammary tumorigenesis can be achieved in the presence of similar circulating levels of estrogen and/or prolactin, whether decreased or increased. These results suggest, therefore, that mechanisms independent of altered secretion of estrogens and/or prolactin are involved in promotion of mammary tumorigenesis by high levels of dietary fat.
在雌性斯普拉格 - 道利大鼠中研究了雌激素和催乳素在高脂（HF）饮食刺激致癌物诱导的乳腺肿瘤中的作用。55日龄时，给大鼠静脉注射5毫克二甲基苯并(a)蒽，5天后，对大鼠进行假手术或双侧卵巢切除。在给予二甲基苯并(a)蒽10天后，将大鼠置于20.0%的高脂饮食或4.5%的对照脂肪（CF）饮食中，然后进行各种药物和内分泌处理，以维持循环雌激素和催乳素水平一致。对假手术完整大鼠和双侧卵巢切除大鼠每日注射氟哌啶醇以增加催乳素分泌、溴隐亭以减少催乳素分泌和/或苯甲酸雌二醇（EB）。与喂食CF饮食的同样处理大鼠相比，喂食HF饮食的完整大鼠乳腺肿瘤发展的所有参数均受到显著刺激。在喂食HF或CF饮食的卵巢切除大鼠中，乳腺肿瘤发展几乎完全受到抑制。当给每日用氟哌啶醇或EB或EB与溴隐亭处理的卵巢切除大鼠喂食HF饮食时，HF饮食增强了乳腺肿瘤发展的一些参数。然而，在所有情况下，与假手术对照大鼠相比，乳腺肿瘤发生均减少。与喂食CF饮食的同样处理大鼠相比，喂食HF饮食并给予EB和氟哌啶醇的卵巢切除大鼠每只大鼠的肿瘤数量显著增加、平均肿瘤大小增加且肿瘤潜伏期缩短。然而，与喂食HF饮食的假对照大鼠相比，这些乳腺肿瘤发生参数仍然降低。这些结果表明，高脂饮食需要足够的循环雌激素和催乳素水平才能在二甲基苯并(a)蒽处理的大鼠中最大程度地促进乳腺肿瘤发生增加。此外，无论雌激素和/或催乳素的循环水平是降低还是升高，在相似的循环水平下，高脂饮食对乳腺肿瘤发生的增强作用都可以实现。因此，这些结果表明，与雌激素和/或催乳素分泌改变无关的机制参与了高水平膳食脂肪促进乳腺肿瘤发生的过程。
