+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Role of cytoprotective mechanisms in the photochemical purging of autologous bone marrow grafts



Role of cytoprotective mechanisms in the photochemical purging of autologous bone marrow grafts



Experimental Hematology 25(7): 629-637



The molecular basis of the differential sensitivity of normal hematopoietic stem cells and of leukemia, lymphoma, and neuroblastoma cells to merocyanine 540 (MC540)-mediated photodynamic therapy (PDT) is not yet completely understood. While the capacity to bind dye molecules appears to be the major determinant of a cell's susceptibility of MC540-mediated PDT, we here present evidence that under certain experimental conditions a cell's capacity to repair MC540-mediated photodynamic damage is also an important factor. Two parameters, temperature and intracellular glutathione (GSH) content, were varied to investigate the role of cellular defense mechanisms in the dye-sensitized photoinactivation of normal murine granulocyte/macrophage progenitors (CFU-GM) and K562, L1210, and melphalan-resistant L1210/L-PAM1 leukemia cells. When exposed to MC540 and light at room temperature, the three leukemia cell lines bound similar amounts of dye and accumulated similar amounts of lipid hydroperoxide (LOOH) but differed markedly in their sensitivity to MC540-mediated PDT. Performing MC540-mediated PDT at 4 degrees C instead of at room temperature reduced dye binding and LOOH generation and enhanced cytotoxicity in some but not all cell lines. A brief (< or = 120 minutes) incubation at 37 degrees C immediately following MC540-mediated PDT accelerated the decay of LOOH in all leukemic cell lines and reduced cell kill by about 2 log in both CFU-GM and leukemia cells. The effect of post-PDT incubation at 37 degrees C on LOOH decay was most pronounced in K562 and least pronounced in L1210/L-PAM1 cells, whereas its effect on cell survival was less pronounced in L1210 cells than in the remaining cell types. L1210/L-PAM1 cells whose GSH content had been reduced from 8.2 to 1.6 micrograms/mg protein by incubation with buthionine sulfoximine recovered from potentially lethal photodynamic damage as rapidly as untreated L1210/L-PAM1 cells and more rapidly than wild-type L1210 cells with a GSH content of 4.5 micrograms/mg protein. Thus, with regard to capacity of L1210/L-PAM1 cells to recover from photodynamic damage, the cells' enhanced capacity to synthesize GSH appeared more decisive than intracellular GSH levels per se. Taken together, these data suggest that temperature-dependent cellular defense mechanisms are significant determinants of a cell's susceptibility to MC540-mediated PDT. The data emphasize the need for temperature control during and immediately after the photochemical purging of autologous bone marrow or peripheral blood stem cells.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 009366347

Download citation: RISBibTeXText

PMID: 9216739


Related references

Triarylmethane dyes as therapeutic agents for the photochemical purging of autologous bone marrow grafts from residual tumor cells. Biophysical Journal 78(1 Part 2): 256A, 2000

Importance of cellular defense mechanisms in the photodynamic purging of autologous bone marrow grafts. Progress in Clinical and Biological Research 389: 147-154, 1994

Effect of molecular structure on the performance of triarylmethane dyes as therapeutic agents for photochemical purging of autologous bone marrow grafts from residual tumor cells. Journal of Pharmaceutical Sciences 89(1): 88-99, 2000

A two-phase approach to B lymphocyte purging of autologous bone marrow grafts for patients with malignant lymphoma contaminated bone marrow. Progress in Clinical and Biological Research 389: 105-109, 1994

Photoradiation methods for purging autologous bone marrow grafts. Progress in Clinical and Biological Research 333: 87, 1990

Evaluation of parameters for purging of autologous bone marrow grafts with 4 hydroperoxycyclophosphamide. Bone Marrow Transplantation 2(Suppl. 2): 147-148, 1987

Deferoxamine as a purging agent for autologous bone marrow grafts in neuroblastoma. Progress in Clinical and Biological Research 377: 71-78, 1992

Immunomagnetic purging of bone marrow grafts for autologous transplantation in neuroblastoma. Acta Clinica Belgica 45(2): 97-106, 1990

Density-gradient separation for 4-hydroperoxycyclophosphamide purging of autologous bone marrow grafts. Progress in Clinical and Biological Research 333: 369-377, 1990

Density gradient separation of autologous bone marrow grafts before ex vivo purging with 4 hydroperoxycyclosphosphamide. Bone Marrow Transplantation 6(5): 321-328, 1990

Optimization of purging of autologous bone marrow grafts for children with precursor B acute lymphoblastic leukemia. Journal of HematoTherapy 6(5): 495-500, 1997

Autologous bone marrow transplantation for acute lymphoblastic leukemia: role of bone marrow purging. Progress in Clinical and Biological Research 389: 125-132, 1994

Purging of autologous bone marrow grafts in children with high-risk neuroblastoma by temporary iron removal. Pediatric Research 37(4 Part 2): 165A, 1994

Ethacrynic acid enhances the merocyanine 540-mediated purging of leukemia cells from autologous bone marrow grafts. Blood 86(10 Suppl. 1): 235A, 1995