Niigata University of Pharmacy & Applied Life Sciences, Department of Functional and Analytical Food Sciences, Higashijima 738-1, Niigata 956-8603, Japan.
Food Funct. 2010 Nov;1(2):174-9. doi: 10.1039/c0fo00102c. Epub 2010 Oct 14.
The present study aims to evaluate the protective effect of squalene against the genotoxicity of the chemotherapeutic agent doxorubicin (Dox) using two genotoxicity assays, the micronucleus assay and the comet assay. Different groups of mice were fed squalene at the doses of 1 and 4 mmol g(-1) body weight (100 or 400 μl as squalene oil) either at 4 h before or 1 h after Dox (20 mg kg(-1)) treatment. 24 h after the Dox treatment, bone marrow erythrocytes were evaluated for the incidence of micronuclei, and the induced DNA strand breaks were examined in heart tissue by the alkaline comet assay. As expected, Dox significantly induced micronuclei in polychromatic (immature) erythrocytes, as well as in total erythrocytes. The frequency of Dox-induced micronucleated erythrocytes was significantly reduced in the mice treated with squalene both before and after Dox administration. Squalene itself obviously did not induce any micronuclei in bone marrow erythrocytes. The comet assay also demonstrated a significant increase in DNA damage, especially DNA single strand breaks in the Dox-treated group of mice as compared to the control. The Dox-induced DNA damage was also effectively reduced by squalene when it was administered either before or after the Dox treatment. Squalene did not induce any significant DNA damage by itself. Compared to the pre-treatment of squalene, post treatment gave rise to more effective prevention against Dox-induced DNA damage. The data suggest that the complimentary use of squalene with Dox will be beneficial to reduce the adverse effect of Dox in cancer chemotherapy, such as the increased incidence of undesirable mutagenic side effects.
本研究旨在通过微核试验和彗星试验这两种遗传毒性检测方法，评估角鲨烯对化疗药物阿霉素（Dox）遗传毒性的保护作用。将不同剂量（1 和 4 mmol g(-1) 体重，即 100 或 400 μl 角鲨烯油）的角鲨烯分别在给予 Dox（20 mg kg(-1)) 前 4 小时或后 1 小时给予各组小鼠。在给予 Dox 24 小时后，检测骨髓红细胞微核的发生率，并通过碱性彗星试验检测心脏组织中诱导的 DNA 链断裂。正如预期的那样，Dox 显著诱导了多色性（未成熟）红细胞和总红细胞中的微核。在给予 Dox 前后给予角鲨烯的小鼠中，Dox 诱导的微核红细胞的频率明显降低。角鲨烯本身在骨髓红细胞中显然没有诱导任何微核。彗星试验还表明，与对照组相比，Dox 处理组的 DNA 损伤明显增加，尤其是 DNA 单链断裂。与 Dox 单独处理组相比，角鲨烯无论是在 Dox 处理前还是处理后给药，都能有效降低 Dox 诱导的 DNA 损伤。角鲨烯本身不会引起任何显著的 DNA 损伤。与角鲨烯的预处理相比，后处理更能有效地预防 Dox 引起的 DNA 损伤。数据表明，角鲨烯与 Dox 联合使用将有利于减少癌症化疗中 Dox 的不良反应，如增加不良诱变副作用的发生率。
