Kim Young Mi, Yang Shihe, Xu Weihong, Li Shibo, Yang Xiaohe
The Department of Pediatrics, the University of Oklahoma Health Sciences Center, OK 73104, USA.
Cancer Genet Cytogenet. 2008 Oct 15;186(2):78-84. doi: 10.1016/j.cancergencyto.2008.06.010.
Genistein is a major soy isoflavone with multiple properties. The impact of soy genistein on breast cancer is controversial. One of the issues is whether soy genistein has a genotoxic effect at physiological concentrations. To address this question using an in vitro model, we first established MCF-10A/G0 and MCF-10A/G1 cell lines, which were MCF-10A cells exposed to 0.01% dimethyl sulfoxide (as vehicle control), i.e., MCF-10A/G0, or 1 micromol/L of genistein for 3 months, MCF-10A/G1, respectively. Chromosomal changes were compared between the two cell lines by routine G-banded chromosome analyses and both regular and array-based comparative genomic hybridization. After 3 months of exposure to genistein, the cell line MCF-10A/G1 showed loss of a normal chromosome 8 and gain of an extra chromosome 20, as well as loss of a chromosomal segment on the short arm of chromosome 9, leading to a homozygous deletion of the tumor suppressor genes CDKN2A (alias p16(INK4a)) and CDKN2B (alias p15(INK4b)). Our results suggest that long-term, low-concentration exposure to genistein may have the potential to induce chromosomal imbalances. These genotoxic effects may work in concert with other factors to induce genetic lesions that contribute to soy- and genistein-associated risk.
染料木黄酮是一种具有多种特性的主要大豆异黄酮。大豆染料木黄酮对乳腺癌的影响存在争议。其中一个问题是，大豆染料木黄酮在生理浓度下是否具有基因毒性作用。为了使用体外模型解决这个问题，我们首先建立了MCF-10A/G0和MCF-10A/G1细胞系，即分别将MCF-10A细胞暴露于0.01%二甲基亚砜（作为溶剂对照）（即MCF-10A/G0）或1微摩尔/升染料木黄酮中3个月得到的MCF-10A/G1。通过常规G带染色体分析以及常规和基于芯片的比较基因组杂交，比较了这两个细胞系之间的染色体变化。在暴露于染料木黄酮3个月后，MCF-10A/G1细胞系显示出一条正常的8号染色体缺失、一条额外的20号染色体增加，以及9号染色体短臂上一个染色体片段的缺失，导致肿瘤抑制基因CDKN2A（别名p16(INK4a)）和CDKN2B（别名p15(INK4b)）的纯合缺失。我们的结果表明，长期低浓度暴露于染料木黄酮可能有诱导染色体失衡的潜力。这些基因毒性作用可能与其他因素协同作用，诱导导致大豆和染料木黄酮相关风险的基因损伤。
