PUVA-induced cell mortality in NCTC 2544 keratinocytes: is it related to the microenvironmental properties of the excited states of psoralens?
The phototoxic effect of psoralen (PSO), 5-methoxypsoralen (5MOP), 8-methoxypsoralen (8MOP) and 4,5',8-trimetylpsoralen (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.
Sousa
C
C
Centro de Química Física Molecular, Instituto Superior Técnico, Lisboa, Portugal.
Melo
T S
TS
Mazière
J C
JC
Santus
R
R
D002460:Cell Line; D011564:Furocoumarins / Q000009:adverse effects*; D015603:Keratinocytes / Q000187:drug effects*; D011701:PUVA Therapy / Q000009:adverse effects*; D012867:Skin / Q000166:cytology / Q000187:drug effects
D011564:Furocoumarins