Induction of apoptosis, depletion of glutathione, and DNA damage by extracorporeal photochemotherapy and psoralen with exposure to UV light in vitro.

Extra corporeal photochemotherapy (ECPT) is a novel treatment for disorders caused by aberrant T lymphocytes. The effects of ECPT were investigated in mononuclear cells (MNC) of six patients suffering from either Sezary syndrome, mycosis fungoides, systemic sclerosis, pemphigus vulgaris or Hodgkin's disease. ECPT caused moderate to severe induction of apoptosis and depletion of glutathione in the MNC of two out of these six patients. The MNC were then treated with 8-methoxypsoralen (8-MOP) and UV light in vitro and analyzed for apoptosis and glutathione levels. 8-MOP and UV light induced a profile of cellular alterations that is similar to ECPT. In addition, we measured DNA damage by means of a PCR-based methodology. As exemplified by the T-cell receptor-delta and glucose-6-phosphate dehydrogenase genes, DNA damage correlated with induction of apoptosis and depletion of glutathione. It is, therefore, reasonable to propose that UV-induced glutathione depletion contributes to DNA lesions which ultimately account for the onset of apoptosis.