The activation of
8-methoxypsoralen (8-MOP) by long-wavelength ultraviolet A light (UVA, 320-400 nm) induces the formation of interstrand cross-links in
DNA.
Psoralen plus UVA (PUVA) is widely used in the treatment of
psoriasis, a hyperproliferative disease of the skin. A new
psoralen plus UVA
therapy has been developed in which the 8-MOP-containing blood of
cutaneous T cell lymphoma (CTCL) patients is irradiated with UVA light extracorporeally (i.e.,
extracorporeal photopheresis). The first group of patients had the leukemic variant of CTCL. A regimen of two treatments on successive days at monthly intervals produced a clinical response in eight of 11 patients. In this review the properties of several
psoralens (both naturally occurring and synthetic derivatives) are compared, using several assays (
DNA cross-linking, inhibition of lymphocyte response to
mitogen stimulation, and cell viability). The development of a panel of
monoclonal antibodies that recognize 8-MOP-modified
DNA is also described. These
antibodies have been used to quantitate
8-MOP photoadduct levels in human
DNA samples. In addition to the
psoralens, the light activation of two other compounds, gilvocarcin and an
insulin-
psoralen conjugate, is described.