Laboratory of Mutagenesis, Institute of Genetics and Biochemistry, Federal University of Uberlândia, Uberlândia (MG), Brazil.
Food Chem Toxicol. 2013 May;55:645-52. doi: 10.1016/j.fct.2013.01.050. Epub 2013 Feb 9.
(-)-Cubebin (CUB) is a lignan isolated from dry seeds of Piper cubeba. We aimed to assess its genotoxic potential and influence on chromosomal damage (frequency of micronuclei - MN) induced by doxorubicin (DXR) in V79 cells and by urethane (URE) in somatic Drosophila melanogaster cells. Our findings indicate an absence of a CUB-mediated genotoxic effect at the concentrations tested. The results also revealed that CUB significantly reduced the frequency of MN induced by DXR, with a mean reduction of 63.88%. In a previous study, our research group demonstrated an absence of CUB-mediated mutagenic effects through the wing Somatic Mutation and Recombination Test (SMART) in Drosophila. In the present study, we used the standard and high bioactivation versions of the SMART to estimate the antigenotoxic effects of CUB associated with URE. At lower concentrations, the recombination level decreased, but at the highest concentration, the recombination level increased. Our data and previous studies suggest that CUB may act as a free radical scavenger at low concentrations, a pro-oxidant at higher concentrations when it interacts with the enzymatic system that catalyzes the metabolic detoxification of DXR or URE, and/or an inducer of recombinational DNA repair.
（-）-毕加林（CUB）是从荜茇干种子中分离得到的木质素。我们旨在评估其遗传毒性潜力及其对阿霉素（DXR）诱导的 V79 细胞和乌来坦（URE）诱导的体细胞黑腹果蝇细胞染色体损伤（微核频率-MN）的影响。我们的研究结果表明，在所测试的浓度下，CUB 没有介导遗传毒性作用。结果还表明，CUB 显著降低了 DXR 诱导的 MN 频率，平均降低了 63.88%。在之前的研究中，我们的研究小组通过黑腹果蝇体细胞突变和重组试验（SMART）证明了 CUB 没有介导的诱变作用。在本研究中，我们使用 SMART 的标准和高生物活化版本来估计 CUB 与 URE 相关的抗原毒性作用。在较低浓度下，重组水平下降，但在最高浓度下，重组水平增加。我们的数据和以前的研究表明，CUB 可能在低浓度下作为自由基清除剂，在与催化 DXR 或 URE 代谢解毒的酶系统相互作用时，在较高浓度下作为促氧化剂，和/或作为重组 DNA 修复的诱导剂。
