Chen Hu, Geng Cui-Zhi, Kuang Gang, Wang Gui-Lan, Fan Zhong-Lin, Wu Xiang-De
Department of General Surgery, The First Affiliated Hospital, Hebei Medical University, Shijiazhuang, Hebei 050013, P. R. China.
Ai Zheng. 2007 Jun;26(6):596-600.
BACKGROUND & OBJECTIVE: As a synthesized estrogenic drug, diethylstilbestrol (DES) is generally used to cure diseases like climacteric period syndrome and osteoporosis due to estrogen insufficient, but its effect on mammary gland epithelial cells is still unclear. This study was to observe the effect of DES on dimethylbenzanthracene (DMBA)-induced carcinogenesis of breast cancer in Wistar rats.
A total of 90 Wistar rats were equally divided into control, DES(1), DMBA, DES(1) plus DMBA, DES(2) plus DMBA, and DES(3) plus DMBA groups. The rats were perfused with DMBA at a dose of 100 mg/kg on Days 1 and 30, and DES at a dose of 0.1 mg x kg(-1) x d(-1) (DES(1)), 0.2 mg x kg(-1) x d(-1) (DES(2)), or 0.4 mg x kg(-1) x d(-1) (DES(3)), respectively. All rats were killed after 44 weeks. The morphology of the breast tissue was observed; silver-binding nucleolar organizer regions (AgNOR) were counted; proliferating cell nuclear antigen (PCNA) staining intensity index (SII), the protein expression of Bcl-2, and C-erbB-2 were detected by SP immunohistochemistry.
Among 15 rats with breast cancer carcinogenesis, 2 came from DES(1) plus DMBA group and 13 from DMBA group. AgNOR count, and the levels of PCNA SII, Bcl-2, and C-erbB-2 were higher in DES(1) group than in control group; AgNOR count, and the levels of PCNA SII, Bcl-2, and C-erbB-2 were significantly lower in DES(2) plus DMBA group than in DES(3) plus DMBA group and DES(1) plus DMBA group (P < 0.05), but there was no significant difference between DES(3) plus DMBA group and DES(1) plus DMBA group (P > 0.05).
Low dose of DES can cause hyperplasia of the mammary gland in Wistar rats but not lead to carcinogenesis. During the DMBA-induced carcinogenesis of breast cancer in Wistar rats, low dose of DES can promote the hyperplasia and carcinogenesis of the mammary gland, medium dose of DES can inhibit the proliferation of mammary epithelial cells, but the effect may weaken while increasing the dose of DES.
己烯雌酚（DES）作为一种合成雌激素药物，常用于治疗更年期综合征、雌激素缺乏所致骨质疏松症等疾病，但其对乳腺上皮细胞的影响尚不清楚。本研究旨在观察DES对二甲基苯并蒽（DMBA）诱导的Wistar大鼠乳腺癌致癌作用的影响。
将90只Wistar大鼠平均分为对照组、DES（1）组、DMBA组、DES（1）+DMBA组、DES（2）+DMBA组和DES（3）+DMBA组。于第1天和第30天，分别以100mg/kg的剂量给大鼠灌注DMBA，以0.1mg·kg⁻¹·d⁻¹（DES（1））、0.2mg·kg⁻¹·d⁻¹（DES（2））或0.4mg·kg⁻¹·d⁻¹（DES（3））的剂量给大鼠灌注DES。44周后处死所有大鼠。观察乳腺组织形态；计数银染核仁组成区（AgNOR）；采用SP免疫组化法检测增殖细胞核抗原（PCNA）染色强度指数（SII）、Bcl-2和C-erbB-2蛋白表达。
在15只发生乳腺癌致癌的大鼠中，2只来自DES（1）+DMBA组，13只来自DMBA组。DES（1）组AgNOR计数及PCNA SII、Bcl-2和C-erbB-2水平高于对照组；DES（2）+DMBA组AgNOR计数及PCNA SII、Bcl-2和C-erbB-2水平显著低于DES（3）+DMBA组和DES（1）+DMBA组（P<0.05），但DES（3）+DMBA组与DES（1）+DMBA组之间差异无统计学意义（P>0.05）。
低剂量DES可导致Wistar大鼠乳腺增生，但不致癌。在DMBA诱导的Wistar大鼠乳腺癌致癌过程中，低剂量DES可促进乳腺增生和致癌，中剂量DES可抑制乳腺上皮细胞增殖，但随着DES剂量增加，该作用可能减弱。
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