Department of Biology, Federal University of Piaui-Teresina, Piaui, Brazil.
Environ Mol Mutagen. 2012 Jan;53(1):51-4. doi: 10.1002/em.20676. Epub 2011 Aug 29.
The aim of this study was to evaluate micronucleus (MN) frequency in polychromatic erythrocytes (PCE) of female rats in persistent estrus (a model developed to mimic polycystic ovary syndrome) treated with selective estrogen receptor modulators (SERMs, tamoxifen, and raloxifene). Forty female Wistar-Hannover rats were divided into four groups of 10 animals each: Group I (normally cycling rats) and Group II (persistent estrus) both received only vehicle, while Group III (persistent estrus) was treated with tamoxifen (250 μg/animal/day) and Group IV (persistent estrus) was treated with raloxifene (750 μg/animal/day). Tamoxifen and raloxifene were given by oral gavage beginning on postnatal day 90 and continuing for 30 consecutive days. Peripheral blood samples were collected from tails 1 day following the last exposure. Blood smears were made on glass slides and stained with 10% Giemsa solution. ANOVA and a Tukey post-hoc test were used for data analysis. Mean percentages of MN were 1.82 ± 0.13, 5.20 ± 0.24, 3.32 ± 0.13, and 3.04 ± 0.12 in Groups I, II, III, and IV, respectively. The results indicate that tamoxifen and raloxifene similarly reduced the formation of MNPCE of female rats in persistent estrus (P < 0.0001 for Groups III and IV vs. Group II), using the dosages and time periods applied in the present study. The data suggest possibly antimutagenic effects of SERMs under high levels of estrogens. The findings also suggest that this is an interesting animal model for studying the genotoxicity of estrogens.
本研究旨在评估经选择性雌激素受体调节剂（SERM，他莫昔芬和雷洛昔芬）处理的处于持续性动情期（模拟多囊卵巢综合征的模型）的雌性大鼠多染红细胞（PCE）中的微核（MN）频率。将 40 只雌性 Wistar-Hanover 大鼠分为四组，每组 10 只：第 I 组（正常动情周期大鼠）和第 II 组（持续性动情期）均仅给予载体，而第 III 组（持续性动情期）用他莫昔芬（250μg/动物/天）处理，第 IV 组（持续性动情期）用雷洛昔芬（750μg/动物/天）处理。从出生后第 90 天开始，通过口服灌胃给予他莫昔芬和雷洛昔芬，连续 30 天。最后一次暴露后 1 天从尾部采集外周血样本。将血液涂片在载玻片上制成，并使用 10％吉姆萨溶液染色。使用 ANOVA 和 Tukey 事后检验进行数据分析。第 I、II、III 和 IV 组的 MN 平均百分比分别为 1.82±0.13、5.20±0.24、3.32±0.13 和 3.04±0.12。结果表明，他莫昔芬和雷洛昔芬以在本研究中应用的剂量和时间段相似地降低了处于持续性动情期的雌性大鼠 MNPCE 的形成（第 III 和 IV 组与第 II 组相比，P<0.0001）。这些数据表明，在高水平雌激素下，SERM 具有可能的抗突变作用。研究结果还表明，这是一种研究雌激素遗传毒性的有趣的动物模型。
