Anomalous effects of dimethyl sulfoxide on the response of the mouse lens and cornea to x-irradiation: "protection" of lens and "sensitization" of cornea.

Abstract

Radiation effects on the eye are of considerable interest from both radiobiologic and radiotherapeutic points of view. They have been the subject of many experimental and clinical investigations. A number of workers (e.g., 1-3) have shown that relatively small doses of ionizing radiation to the lens can cause posterior lenticular opacities. Relatively large, repeated exposures result in late corneal lesions (4). In clinical situations irradiation of the eye is avoided, if possible, by appropriate direction of the beam and by use of shields. Elaborate technics for shielding the eye during irradiation of the periorbital region with high-energy electrons have been reported (5, 6). In many instances, however, all scattered radiation cannot be prevented from entering the eye. Much work has been done on chemical protection of the lens against effects of ionizing radiation. Cysteine administered intravenously is an effective protector against radiation cataract (7), but when given by subconjunctival injection exerts only a moderately protective influence (8). Other substances, e.g., glutathione, are also somewhat effective in reducing radiation damage to the lens when given by intravenous injection (8). To our knowledge, no substance administered topically to the eye has been reported to protect the lens from radiation damage. Local lenticular protection, as opposed to systemic protection, would have the inherent advantage of reducing radiation damage to the lens while not affording concomitant protection to nearby tissue (e.g., periorbital tumors). In addition, protection by topical administration would be far simpler than the complex shielding technics otherwise required. Three properties of dimethyl sulfoxide (DMSO) suggested its possible use in topical application for protection of the lens from the damaging effects of ionizing radiation. First, it passes easily through biological membranes and even through intact skin (9, 10). Second, DMSO has been shown to be a radioprotective substance at levels of the animal (ll), the cell (12), and the molecule (13). Third, it can act as a penetrant carrier for other organic molecules (14), perhaps for a protector such as 13mercaptoethylamine (MEA).