MacGregor J T, Wehr C M, Manners G D, Jurd L, Minkler J L, Carrano A V
Mutat Res. 1983 Dec;124(3-4):255-70. doi: 10.1016/0165-1218(83)90197-0.
No consistent increases in the micronucleus frequency were observed in bone marrow or peripheral blood erythrocytes from mice treated with quercetin, rhamnetin, neohesperidin dihydrochalcone, or hesperetin dihydrochalcone under various exposure and sampling conditions. Over the dose range of 100-1000 mg/kg, quercetin failed to increase significantly erythrocyte micronucleus frequencies either (1) in bone marrow of male mice at 6 h after the second of 2 i.p. or oral doses given 24 h apart, or at 48, 96 or 192 h after a single i.p. or oral dose, or (2) in peripheral blood of male or female mice sampled for 7 consecutive days following a single i.p. dose. Feeding 5% or 10% quercetin for 8 days also failed to increase the micronucleus frequency in bone marrow erythrocytes of female or male mice. Hesperetin dihydrochalcone and neohesperidin dihydrochalcone, at p.o. doses of 100-1000 mg/kg, did not increase the micronucleus frequency in bone marrow erythrocytes 6 h after the second of 2 doses 24 h apart, nor did rhamnetin at 48 or 96 h after a single i.p. dose of 1000 mg/kg. Galangin, in contrast, did significantly increase the micronucleus frequency in bone marrow and blood erythrocytes under certain conditions, but the largest increases were only between 2 and 3 times control values and these were observed at highly toxic doses. Rabbits given up to 250 mg/kg quercetin i.p. showed no treatment-related increase in the sister-chromatid-exchange frequency in peripheral blood lymphocytes sampled at 1 and 7 days after treatment. These results fail to confirm published data which report a markedly increased frequency of micronuclei in bone marrow erythrocytes from quercetin-treated mice, show no quercetin-related alterations in the sister-chromatid-exchange frequency in rabbit lymphocytes, and indicate that clastogenesis in bone marrow erythroblasts due to oral or i.p. administration of the flavonols studied is at most very weak.
在各种暴露和采样条件下，用槲皮素、鼠李素、新橙皮苷二氢查耳酮或橙皮素二氢查耳酮处理的小鼠，其骨髓或外周血红细胞中的微核频率未观察到持续增加。在100 - 1000 mg/kg的剂量范围内，槲皮素也未能显著增加红细胞微核频率：(1) 在间隔24小时腹腔注射或口服2次，第二次给药后6小时的雄性小鼠骨髓中，或单次腹腔注射或口服给药后48、96或192小时的雄性小鼠骨髓中；(2) 在单次腹腔注射给药后连续7天采样的雄性或雌性小鼠外周血中。用5%或10%的槲皮素喂养8天，也未能增加雌性或雄性小鼠骨髓红细胞中的微核频率。橙皮素二氢查耳酮和新橙皮苷二氢查耳酮，口服剂量为100 - 1000 mg/kg时，在间隔24小时的2次给药中的第二次给药后6小时，未增加骨髓红细胞中的微核频率；1000 mg/kg单次腹腔注射给药后48或96小时，鼠李素也未增加微核频率。相比之下，高良姜素在某些条件下确实显著增加了骨髓和血液红细胞中的微核频率，但最大增幅仅为对照值的2至3倍，且这些是在高毒剂量下观察到的。腹腔注射高达250 mg/kg槲皮素的兔子，在治疗后1天和7天采样的外周血淋巴细胞中，未显示出与治疗相关的姐妹染色单体交换频率增加。这些结果未能证实已发表的数据，即报告槲皮素处理的小鼠骨髓红细胞中微核频率显著增加，未显示槲皮素相关的兔淋巴细胞姐妹染色单体交换频率改变，并表明口服或腹腔注射所研究的黄酮醇导致的骨髓成红细胞中的断裂发生至多非常微弱。
