Effect of multidrug-resistant P-glycoprotein gene expression on chloroaluminum tetrasulfonate phthalocyanine concentration.

The effect of multidrug-resistant P-glycoprotein gene expression (MDR1) in 3T3 cells on cellular concentrations and cytotoxicity induced by the photodynamic agent chloroaluminum tetrasulfonate phthalocyanine (AlSPc) was evaluated. 3T3 cells transfected with a retroviral vector expressing human MDR1 cDNA were resistant to colchicine. Resistant cells incubated with daunomycin accumulated only 40-50% of the quantity of daunomycin accumulated in control cells. Resistant cells incubated with daunomycin in the presence of verapamil had intracellular daunomycin concentrations approximately equal to control cells without verapamil. When these MDR1 3T3 cells were incubated with AlSPc, cellular concentrations of AlSPc did not differ between cells resistant to colchicine and those that were not. Similarly, there was little difference in cytotoxicity demonstrated by 51Cromium release in the two cell lines exposed to AlSPc and light (675 nm; 6 J/cm2). This study suggests photodynamic therapy using AlSPc may be a useful treatment modality for tumors in which the MDR1 P-glycoprotein confers resistance to cancer chemotherapeutics.

Effects of recombinant canine granulocyte colony-stimulating factor on white blood cell production in clinically normal and neutropenic dogs.

Recombinant canine granulocyte colony-stimulating factor (rcG-CSF) was administered to clinically normal dogs, cyclic-hematopoietic dogs, and dogs undergoing autologous bone marrow transplantation, to determine whether rcG-CSF could be used to stimulate WBC production and function in normal and neutropenic dogs. To the normal dogs, rcG-CSF was administered by SC injection at rates of 1 microgram/kg of body weight, q 12 h; 2 micrograms/kg, q 12 h; or 5 micrograms/kg, q 12 h. A significant dose-dependent increase in the WBC count resulted from the stimulation of bone marrow progenitor cells. The increased WBC count was characterized by mature neutrophilia and monocytosis. Neutrophil myeloperoxidase and phagocytic activity were normal in rcG-CSF-treated normal dogs, demonstrating the production of normal functional neutrophils in response to rcG-CSF treatment. Recombinant canine G-CSF prevented neutropenia and associated clinical signs but did not completely eliminate the cycling of neutrophils in cyclic-hematopoietic dogs when it was administered at rates of 1 microgram/kg, q 12 h, and 2.5 micrograms/kg, q 12 h. The time to bone marrow reconstitution was not decreased in dogs treated with rcG-CSF at a rate of 2.5 micrograms/kg, q 12 h, for 13 days following autologous bone marrow transplantation. On the basis of our findings, we suggest that treatment with rcG-CSF is an effective way to stimulate myelopoiesis in dogs, but that the dose of rcG-CSF required to stimulate WBC production will vary depending on the cause of neutropenia. Recombinant canine G-CSF should be useful in stimulating production and maintaining function of WBC for treatment of clinical diseases seen commonly in veterinary practice.