Assessment of the cytostasis and chromosomal instability potential of myricetin and its chemopreventive effect against bleomycin-induced cyto-genotoxicity.

Myricetin (ME) is a major constituent of various foods and beverages consumed by humans, including vegetables, teas and fruits, and is primarily recognized for its iron-chelating, antioxidant, anti-inflammatory and anti-cancer properties. This study evaluated the cytostatic, genotoxic, and chemopreventive effects of ME in CHO-K1 cells using the Cytokinesis-Block Micronucleus (CBMN) assay and explored molecular interactions through in silico systems biology analysis. CHO-K1 cells were exposed to ME (2.5-40 µM). Cytostasis was assessed by the Cytokinesis-Block Proliferation Index (CBPI), and chromosomal instability was measured by the frequency of micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs). ME at 40 µM significantly reduced CBPI, while concentrations of 20 and 40 µM increased chromosomal instability (p < 0.05). For chemoprevention, ME (2.5-10 µM) was administered in pre-, co-, and post-treatment with bleomycin (BLM). ME significantly reduced BLM-induced MNi and NPBs in all protocols (p < 0.05). In silico analysis revealed strong interactions between ME and key proteins related to DNA damage response, apoptosis, and bleomycin detoxification. Notably, the in silico analysis revealed a strong association between ME and bleomycin hydrolase (BLMH) and the interaction of ME with proteins related to DNA damage response and apoptosis regulation. Overall, ME exhibited genotoxicity at high concentrations but demonstrated a significant chemopreventive effect at lower, nontoxic doses. These findings provide insights into the dual biological activity of ME and support its potential use as a protective agent against genotoxic damage.