Comparative toxicological responses of cancer and normal cells to silver nanoparticles: Roles of oxidative stress and DNA damage.

Silver nanoparticles (AgNPs) are among the most widely studied nanomaterials for anticancer applications. Their ability to induce selective cytotoxicity in cancer cells relative to normal cells has attracted significant scientific interest. This study compared the toxicological responses of human breast cancer cells (MCF-7) and non-tumorigenic mammary epithelial cells (MCF-10A) to biologically synthesized AgNPs (mean diameter 18 ± 3 nm). Cell viability, reactive oxygen species (ROS) generation, antioxidant enzyme activity, DNA damage parameters, mitochondrial membrane potential, and apoptosis markers were evaluated across a concentration range of 5 to 160 μg/mL. AgNPs reduced MCF-7 viability with an IC50 of ~35 μg/mL, while MCF-10A cells required ~170 μg/mL for equivalent inhibition, yielding a selectivity index of 4.1 at 72 h. ROS levels in MCF-7 cells increased 9.2-fold at 80 μg/mL versus 3.9-fold in MCF-10A. Comet assay confirmed greater DNA strand breaks in MCF-7 cells (74% tail DNA) than MCF-10A (38.5%). Antioxidant enzymes were markedly depleted in cancer cells but partially retained in normal cells. Apoptosis analysis revealed caspase-3 activation 2.5-fold higher in MCF-7 than MCF-10A. Mechanistically, diminished antioxidant capacity and defective DNA repair in cancer cells underlie differential sensitivity. These findings support AgNPs as a selective anticancer agent and provide a mechanistic framework for nanoparticle-based therapeutic development.