Cellular aspects of phototoxic reactions induced by kynurenic acid. II. Fine structural analysis and cytochemistry on cultivated cells.

A recent report described the establishment of an experimental model for studying photo-oxidative damage inflicted by kynurenic acid on cultivated cells. Preliminary findings by scanning electron microscopy (SEM) were reported. For the present paper supplementary SEM studies were performed, and it was found that maximum cell damage appears 2 to 4 hours post irradiation. With low concentrations of kynurenic acid and brief UVA exposure, repair mechanisms seem to occur. Damage in the form of cellular swelling and plasma membrane alterations is most easily recognized by SEM, which is far more sensitive than ordinary light microscopy. Transmission electron microscopy (TEM) reveals morphologic alterations, consisting of an enhanced formation of endocytotic vacuoles from the plasma membranes, swelling with disruptions of the cell sap continuity, mitochondrial swelling, dilatation of the endoplasmic net, and vesiculation of some of the microvilli. Lysosomal damage, which was not seen until very late post irradiation and only for high concentrations of kynurenic acid and long-term UVA exposure, seems to be a secondary phenomenon. This hypothesis is further supported by the cytochemical analysis. The primary event thus seems to affect the plasma membrane level and originate in the binding of kynurenic acid to the plasma membrane on which subsequent UVA irradiation inflicts secondary intracellular alterations due to increased permeability and swelling.