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PUVA‐Induced Cell Mortality in NCTC 2544 Keratinocytes: Is It Related to the Microenvironmental Properties of the Excited States of Psoralens?
Author(s) -
Sousa Cristina,
Melo Teresa Sá e,
Mazière JeanClaude,
Santus René
Publication year - 1998
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1998.tb09094.x
Subject(s) - lipid peroxidation , psoralen , phototoxicity , chemistry , puva therapy , biophysics , biochemistry , intracellular , cell , cell membrane , cell culture , membrane , in vitro , immunology , oxidative stress , biology , dna , genetics , psoriasis
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.