In order to determine the specific effects of radical-induced reactions in the absence of complicating excited-state pathways, four different thiohydroxamic
esters and their parent molecule, N-hydroxypyridine-2(1H)-thione, have been studied in murine
L1210 leukemia cells for their ability to produce photobiological damage. Irradiation (lambda exc = 355 nm) of cells in the presence of thiopyridone
esters, specific photolytic precursors of
sulfur-,
carbon- and
oxygen-centered radicals, caused toxicity that was unambiguously demonstrated to result from radical
photosensitization mechanisms. Cellular morphological changes were observed following irradiation but apoptosis was not found to take place. A good correlation was evident between lipid peroxidation, measured by the
thiobarbituric acid method, and
phototoxicity, assessed by the
trypan blue exclusion assay, indicating that the
ester derivatives exert their effects mainly in plasma and/or subcellular membranes. Irradiation performed under deaerated conditions also induced significant
phototoxicity but the effects of deaeration were dependent on the
ester used and are discussed in terms of the nature of the primary radical species generated in each case. Irradiation of L1210 cells in the presence of N-hydroxypyridine-2(1H)-thione, a nonspecific, photochemical source of
hydroxyl radical, was also found to trigger
phototoxicity and lipid peroxidation. However in this case, photodamage cannot yet be definitely attributed to a radical or type II mechanism although the apparent
oxygen independence of
phototoxicity would indicate that type II contribution is not significant.