The biphasic-dose response of microorganisms to hydrogen peroxide is a phenomenon of particular interest in hormesis research. In different animal models, the dose-response curve for ethanol is also nonlinear showing an inhibitory effect at high doses but a stimulatory effect at low doses. In this study, we observed the hormetic-dose response to ethanol in budding yeast S. cerevisiae. Cross-protection is a phenomenon in which exposure to mild stress results in the acquisition of cellular resistance to lethal stress induced by different factors. Since both hydrogen peroxide and ethanol at low concentrations were found to stimulate yeast colony growth, we evaluated the role of one substance in cell cross-adaptation to the other substance as well as some weak organic acid preservatives. This study demonstrates that, unlike ethanol, hydrogen peroxide at hormetic concentrations causes cross-resistance of S. cerevisiae to different stresses. The regulatory protein Yap1 plays an important role in the hormetic effects by low concentrations of either hydrogen peroxide or ethanol, and it is involved in the yeast cross-adaptation by low sublethal doses of hydrogen peroxide. 1. Introduction Organisms’ adaptation to environmental stress has become a subject of great interest over the last decades [1–5]. Like other organisms, budding yeast Saccharomyces cerevisiae has developed several strategies to survive stressful changes in their environment. Sudden challenge can result in disturbance of cellular functions or even cell death. Clearly, yeast cells respond rapidly and modify their internal systems to prevent dramatic events. Depending on the intensity and type of stress, many different mechanisms contribute to the development of yeast resistance to stressful changes. It is widely believed that cell exposure to mild stress results in the acquisition of cellular resistance to further lethal stress, what is called “adaptive response” or “preadaptation” [6, 7]. The phenomenon has been observed in various organisms: from bacteria to humans. In many cases, an exposure to mild stress develops tolerance not only to higher doses of the same stressor but also to stress caused by other factors. This phenomenon, known as “cross-protection” or “cross-adaptation” [6, 7], suggests the existence of complex mechanisms, which sense and respond to different kinds of stress. The literature includes data on S. cerevisiae general response, pre-adaptation, and cross-adaptation to extreme temperatures, osmotic shock, and oxidative stress [2, 6, 8–12]. There is information on the increased
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