PUVA Treatment Selectively Induces a Cell Cycle Block and Subsequent Apoptosis in Human T‐Lymphocytes

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Abstract
Psoralen plus UVA (320–400 nm radiation; PUVA) is a highly effective therapy for cutaneous diseases caused by skin infiltration with normal or neoplastic T‐lympho‐cytes. In comparing the effects of pharmacologically relevant, low‐dose PUVA treatment on growth of human keratinocytes, peripheral blood leukocytes (PBMC), and T‐lymphocyte cell lines, we determined that PBMC or T‐lymphocytes were >50‐fold more sensitive to cytotoxic effects of PUVA, while antiproliferative effects were produced by similar PUVA levels in all cell types. Low doses of PUVA (10 ng/mL 8‐methoxypsoralen and 1–2 J/cm2) were highly cytotoxic for phytohemagglutinin‐activated normal lymphocytes or transformed T‐lymphocytes as assessed by two viability assays and by flow cytofluo‐rometry. Altered lymphocyte morphology, nuclear fragmentation, TUNEL+ nuclei or nuclear fragments, and the appearance of a sub‐G, DNA peak indicated that cell death occurred by apoptosis, beginning about 1 day after PUVA treatment and continuing for several days thereafter. From assessment of cell cycle progression in mi‐mosine‐synchronized cells, PUVA treatment markedly slowed cell cycle progression, eventually producing cell cycle arrest and apoptotic entry. We propose that the probable basis for disease remissions (psoriasis, cutaneous T‐cell lymphoma) produced by PUVA treatment is through selective cytotoxic effects on clonal T‐lymphocyte populations that are concentrated in diseased skin.

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