Grubbs C J, Juliana M M, Whitaker L M
Nutrition Sciences Department, University of Alabama, Birmingham 35294.
Anticancer Res. 1988 Jan-Feb;8(1):113-7.
Because previous data had suggested that short-term treatment with pharmacological doses of estradiol and progesterone might be an effective means of preventing mammary cancer initiation, additional experiments were performed to confirm this observation and to determine if lower doses of the hormones would also have chemopreventive activity. Rats treated with the steroids for five weeks and administered the carcinogen (methylnitrosourea) three weeks later were observed for one year for the appearance of mammary cancers. Hormone pretreated rats exhibited a reduction in number of mammary cancers of approximately 90% from rats receiving the steroid vehicle. During the extended observation period, treatment with steroids did not induce gross or histological lesions in any tissues. In a separate experiment, decreasing the dose levels from 20 micrograms estradiol plus 4 mg progesterone to 5 mg estradiol plus 2 mg progesterone did not significantly alter the chemopreventive efficacy of the treatment regimen. Differentiation of the mammary gland to a secretory state with hormones apparently alters the epithelial cells so that, even after involution has occurred, the gland maintains its resistance to a carcinogenic insult.
因为先前的数据表明，用药理剂量的雌二醇和孕酮进行短期治疗可能是预防乳腺癌发生的有效方法，所以进行了额外的实验来证实这一观察结果，并确定较低剂量的激素是否也具有化学预防活性。用类固醇治疗五周，三周后给予致癌物（甲基亚硝基脲）的大鼠被观察一年，以观察乳腺癌的出现情况。激素预处理的大鼠与接受类固醇载体的大鼠相比，乳腺癌数量减少了约90%。在延长的观察期内，类固醇治疗未在任何组织中诱发肉眼可见或组织学病变。在一项单独的实验中，将剂量水平从20微克雌二醇加4毫克孕酮降至5毫克雌二醇加2毫克孕酮，并未显著改变治疗方案的化学预防效果。用激素使乳腺分化为分泌状态显然会改变上皮细胞，这样即使在退化发生后，腺体仍保持对致癌损伤的抵抗力。
