Continuous in Vitro Exposure to Low-dose Genistein Induces Genomic Instability in Breast Epithelial Cells

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.