Heavy water toxicity via isotope effects: Stronger than high-dose radiation, neutralized by light water

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Numerous enzymatic reactions involve hydrolysis, making water indispensable for sustaining life. Some water includes hydrogen isotopes, deuterium or tritium, with larger atomic weights. Heavy water consisting of deuterium is toxic to living organisms and induces cell death; however, the extent and underlying mechanisms of this toxicity remained elusive. Herein, we demonstrate that 100% heavy water triggers a remarkably heightened apoptotic response in human cells, compared to exposure to high-dose ionizing radiation. This pronounced effect of heavy water on cellular function may stem from the quantum-level mechanisms of kinetic isotope effects inherent to water isotopes, leading to a deceleration in enzymatic hydrolysis reactions. Notably, dilution of heavy water by approximately ten-fold with ordinary light water abolishes its isotope effect on enzymatic hydrolysis reactions, concomitant with the disappearance of DNA repair inhibition and cell death induction in human cells. These findings reveal that high concentrations of water isotopes containing heavier hydrogen have extreme cell death-inducing toxicity, yet this toxicity disappears upon dilution, thereby offering crucial insights into environmental considerations.