PUVA-Induced Cell Mortality in NCTC 2544 Keratinocytes: Is It Related to the Microenvironmental Properties of the Excited States of Psoralens? |
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Authors: | Cristina Sousa Teresa Sá e Melo Jean-Claude Mazière René Santus |
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Institution: | Centro de Quirnica Fisica Molecular, Instituto Superior Técnico, Lisboa, Portugal;Laboratoire de Biochimie, Universitéde Picardie Jules Verne, Amiens, France;Muséum National d'Histoire Naturelle, Laboratoire de Photobiologie, Paris, France |
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Abstract: | The phototoxic effect of psoralen (PSO), 5-methoxypsoralen (5MOP), 8-methoxypsoralen (8MOP) and 4,5',8-trimethylpsoralen (TMP) has been compared on the NCTC 2544 keratinocyte cell line in terms of cell mortality and lipid peroxidation. The order of effectiveness for cell photokilling is TMP, 5MOP >> 8MOP, PSO, whereas a little lipid peroxidation is observed for the four psoralens under study. Oxygen-independent membrane damage seem to play a key role in the lethal photodamage because the biological effectiveness of the most hydrophobic lipid-soluble psoralens, TMP and 5MOP, is about an order of magnitude higher than that of the more water-soluble 8MOP and PSO. In relation to this hypothesis, and in contrast to 8MOP, TMP is readily extracted from cells by ethyl acetate, a good membrane solvent, as shown by GC/MS analysis on cell extracts. The results are discussed in terms of the highly microenvironment-dependent photophysical properties of psoralens. By the measure of the intracellular psoralen concentration, the neutral red uptake and the lipid peroxidation products, this work provides evidence that PUVA therapy-mediated cell mortality is a lipid peroxidation-independent phenomenon. |
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