1. Demonstration of differences in drug resistance by direct testing of DNA excision repair activity following standard and liposomal daunorubicin exposure in normal paediatric marrow using high resolution CLSM.
- Author
-
Lannon CL, Ball LM, Pyesmany AF, Yhap M, Langley GR, and van Velzen D
- Subjects
- Antibiotics, Antineoplastic administration & dosage, Bone Marrow Cells cytology, Bone Marrow Cells physiology, Cells, Cultured, Child, Daunorubicin administration & dosage, Drug Carriers, Humans, Liposomes, Reference Values, Sensitivity and Specificity, Antibiotics, Antineoplastic toxicity, Bone Marrow Cells drug effects, Comet Assay methods, DNA Damage, DNA Repair drug effects, Daunorubicin toxicity, Microscopy, Confocal methods
- Abstract
Background: High resolution Confocal Laser Scanning Microscopy (CLSM) may be applied to testing of drug resistance in vitro in clinical setting. Rapid analysis of DNA damage by precise quantitation of excised DNA in bone marrow samples exposed to potential treatment moieties directly after isolation but the relative sensitivity of the integrated method is as yet untested., Aims: To test the clinical applicability of SCGE/high resolution CLSM for differences in drug resistance in marrow cells., Methods: Cells from normal bone marrow samples were exposed for identical periods and at 4 concentrations to either 1 hour of standard Daunorubicin (.5, 1, 1.5, 2 micrograms/ml) or 8 hours DaunoXome (courtesy of NeXstar Inc, USA) (.05, .1, .15, .2 microgram/ml). After 2 and 6 hours recovery, cells were harvested for SCGE, randomization, analysis of tail length, total excised DNA and fragment size distribution using high resolution CLSM., Results: Tail length and fragment size distribution was not, but total excised DNA was significantly increased after 0.1 microgram/ml Liposomal Daunorubicin (DaunoXome) compared to 1.0 microgram/ml Daunorubicin., Conclusion: SCGE/high resolution CLSM effectively demonstrated differences in Daunorubicin resistance of human marrow cells to alternative formulations. The method has potential for use in clinical testing of neoplastic cell drug resistance.
- Published
- 1999
- Full Text
- View/download PDF