Singlet Dioxygen ¹O₂, its Generation, Physico-Chemical Properties and its Possible Hormetic Behavior in Cancer Therapy

Abstract

Singlet dioxygen 1O2 is one excited state among the three other possible spectroscopic states of molecular oxygen. Here, we first describe the use of published spectroscopic data and thermodynamic modeling based on irreversible entropy production. Such concepts are further applied to the synthesis of singlet dioxygen and its reactions with crucial biological molecules. In a last section, we suggest that singlet dioxygen and ozone may be responsible for the success of radiation therapy, that has been used to treat cancer successfully for over 120 years. Its precise mechanism of action remains controversial. We thus aim to clarify the role of singlet oxygen in radiotherapy and chemotherapy. A partial conversion of ionizing radiation in the body into thermal photons could be assumed. The antitumor effect may involve these thermal photons, such as the one delivered by red/infrared sources. Thermal photons (wavelengths of 635 nm and 1270 nm) convert triplet dioxygen into singlet dioxygen by changing the spin of its outer electrons. Despite its short half-life, Singlet dioxygen is responsible for the activation of multiple free radicals (such as hydrogen peroxide), which may target proteins and DNA, induce either apoptosis or oxidative phosphorylation. At moderate concentrations, thermodynamic data suggests that singlet dioxygen may readily react with water to form a potent pro-apoptotic molecule (ozone), thus decreasing cancer growth. However, at high concentration cytotoxic effects against all kind of cells occurs. This strongly suggests a non-linear hormetic behavior of singlet dioxygen. It is also proposed that cytotoxic chemotherapy induces the same free radicals that singlet dioxygen does. There are also other ways to enhance the production of singlet dioxygen, such as phototherapy using Methylene Blue for instance. As a source of reactive oxygen species (ROS), singlet oxygen could thus be a common agent active both in radiotherapy and chemotherapy. It is probable that the activity of radiation therapy and chemotherapy may be mediated by the conversion of triplet to singlet oxygen. This may explain the oxygen effect such as described in radiotherapy and chemotherapy.