Selective cytotoxicity of low-density lipoprotein to helper T cells of cutaneous T-cell lymphoma after photoperoxidation with 8-methoxypsoralen.
Lymphocyte-containing plasma subjected to photolysis in the presence of 8-methoxypsoralen (methoxsalen, 8-MOP) has previously been shown to be effective against cutaneous T-cell lymphoma and the AIDS-related complex. The mechanism of this effect was thought to involve photoreaction of 8-MOP with DNA, based on certain in vitro experiments. The results of this study suggest a different mechanism. Low-density lipoprotein (LDL) from fresh human plasma was photosensitized by addition of 8-MOP and exposure to UV light (mp-LDL), and the reactions of the LDL lipids and the chemical actions induced by these reactions were monitored. In a separate procedure, LDL was peroxidized with hydrogen peroxide and peroxidase (p-LDL). mp-LDL and p-LDL were then tested in cytotoxicity assays on HuT-78 helper T cells of cutaneous T-cell lymphoma. These results indicate that (a) LDL in plasma in the presence of very low concentrations of 8-MOP (200 ng/mL) can be peroxidized by UV light; (b) this photoperoxidized LDL is cytotoxic to helper T cells of cutaneous T-cell lymphoma in a dose-dependent manner; but (c) it does not kill normal lymphocytes under similar conditions. The findings also suggest alternative therapeutic strategies for treatment of cutaneous T-cell lymphoma, such as direct utilization of peroxidized LDL.
Fossel
E T
ET
Department of Radiology, Charles A. Dana Research Institute, Beth Israel Hospital, Boston, MA 02215.
Fletcher
J G
JG
McDonagh
J
J
Hui
K K
KK
D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000528:radiation effects* / Q000633:toxicity; D008730:Methoxsalen / Q000494:pharmacology*; D010778:Photochemotherapy; D012751:Sezary Syndrome / Q000188:drug therapy* / Q000276:immunology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D008077:Lipoproteins, LDL; D008730:Methoxsalen