Effects of psoralens plus ultraviolet radiation on human lymphoid cells in vitro

Photochemotherapy with oral 8-methoxypsoralen (8-MOP) plus long wavelength UV radiation (UVA) has been shown to affect lymphoid cells circulating through the skin. An in vitro assay was developed to mimic some of the therapeutic parameters of 8-MOP concentration and UVA exposure estimated to impinge upon lymphoid cells. In vitro treatment with these presumed therapeutic levels of 8-MOP plus UVA induced a level of inhibition of lymphoid cell DNA synthesis similar to that observed in vivo. Furthermore, the DNA synthesis inhibition was associated with DNA interstrand cross-link induction, reduced cell survival, and impaired immune reactivity. This assay predicts that such effects would be induced in vivo. A lymphoblastoid cell line from a patient with Cockayne's syndrome was shown to be hypersensitive to killing by radiation (280-320 nm) from a fluorescent sunlamp (UVB) but to have normal survival after treatment with 8-MOP plus UVA. Thus there is at least one major UVB recovery pathway in human cells that is different from the recovery pathway for 8-MOP plus UVA damage and leads us to believe that combined treatment with UVB and 8-MOP plus UVA may have a greater effect than either treatment alone.