Dose-Dependent Protective and Inductive Effects
of Xanthohumol on Oxidative DNA Damage in
Saccharomyces cerevisiae

The effect of xanthohumol, a prenylflavonoid isolated from the hop plant (Humulus lupulus L.), on Saccharomyces cerevisiae DNA oxidative damage and viability was evaluated. Yeast cultures under oxidative stress, induced by H₂O₂, displayed stronger growth in the presence of 5 mg/L of xanthohumol than cultures with only H₂O₂. Likewise, DNA damage assessed by the comet assay was significantly lower in cells co-incubated with xanthohumol and H₂O₂. Accordingly, fluorescence of dichlorofluorescein in cells treated with H₂O₂ and xanthohumol was considerably lower than in cells exclusively treated with H₂O₂, indicative of a reactive oxygen species scavenging mechanism and consequent formation of oxidation products, as detected by mass spectrometry. However, at concentrations above 5 mg/L, xanthohumol elicited an opposite effect, leading to a slower growth rate and significant increase in DNA damage. A yeast yap1 deletion mutant strain sensitive to oxidative stress grew more slowly in the presence of at least 5 mg/L of xanthohumol than cultures of the wild type, suggesting that xanthohumol toxicity is mediated by oxidative stress. This evidence provides further insight into the impact of xanthohumol on yeast cells, supporting dose-dependent antioxidant/antigenotoxic and prooxidant/genotoxic effects.