Genetic variability in the response of normal murine hematopoietic progenitor cells to extracorporeal photochemotherapy

Normal hematopoietic progenitor cells from 129S6/SvEv mice are substantiall y less sensitive to Merocyanine 540 (MC540)-mediated photodynamic therapy ( PDT) than hematopoietic progenitors from sex- and age-matched C57BL/6 mice. When exposed to a combination of MC540 and Light commonly used for the ext racorporeal purging of hematopoietic stem cells, granulocyte/macrophage pro genitors (CFU-GM) from C57BL/6 mice are depleted 7.9-fold whereas CFU-GM fr om 129S6/SvEv and (C57BL/6 x 129S6/SvEv) Fl mice are depleted 1.4- and 2-fo ld, respectively. The same rank order of sensitivity is also found with reg ard to unipotent progenitors of granulocytes and macrophages and with regar d to early and late erythroid progenitors. The resistance of hematopoietic progenitors from 129S6/SvEv mice to MC540-PDT appears to be the result of r educed dye binding rather than the result of high levels of intracellular g lutathione. These findings have practical implications for the design of pr eclinical tests of PDT in animal models. They may also provide a useful too l for future investigations into the molecular determinants of sensitivity to MC540-PDT.