IN-VITRO PHOTOINHIBITION BY PSORALEN AND ULTRAVIOLET-A RADIATION OF HUMAN HEMATOPOIETIC PROGENITORS

The in vitro sensitivity of human hematopoietic progenitors to PUVA, 8 -MOP and UVA alone was investigated. 8-MOP alone at final concentratio ns of 150, 200, 600 and 1000 ng/ml did not modify colony growth of cir culating and bone marrow erythroid (BFU-E), myeloid (CFU-GM) and immat ure (CFU-GEMM) hematopoietic progenitors obtained from normal controls . The exposure of the same progenitors to increasing doses of UVA, up to 12 J/cm(2), progressively decreased hematopoietic colony growth (wi th estimated 50% inhibition occurring at about 5 J/cm(2)). In vitro PU VA treatment (8-MOP 200 ng/ml followed by UVA 5 J/cm(2)) caused 90% gr owth inhibition of circulating and bone marrow hematopoietic progenito rs. In addition, the treatment completely inhibited the formation of s pontaneous erythroid colonies, obtained from 5 polycythemic patients, that an considered to be a marker of this neoplastic disease. PUVA cyt otoxicity was assessed by the colorimetric MTT assay. The percentage o f cell death after PUVA exposure was 29+/-10% for both peripheral and bone marrow mononuclear cells. Our findings indicate that 8-MOP alone is not toxic to hematopoietic progenitors whereas WA treatment determi nes in vitro a dose-dependent inhibition of the clonogenic capacity of normal hematopoietic cells. PUVA treatment enhances this effect, caus ing a quite complete inhibition of hematopoietic progenitors colony fo rmation from normal donors and spontaneous BFU-E colony formation from polycythemic patients.