ABSTRACT
Cytotoxic effects of sequential taxol (paclitaxel) and X-irradiation on drug-sensitive human cultured promyelocytic leukemia (HL-60) cell line and its multidrug-resistant sublines were examined using photometric MTT test and flow cytometry. Paclitaxel (at concentrations 1-10 nmol) stimulated the cytotoxic effect of irradiation in HL-60 and to a lesser extent also in HL-60/ADR, but not in HL-60/VCR cells. The stimulation of radiation-induced cytotoxic effect by paclitaxel correlated with its potential to induce cell cycle and viability alterations identified with flow cytometric analysis (i.e. increased propidium iodide staining, increased side scatter, decreased forward angle scatter, accumulation of necrotic cell detritus, apoptotic pre-G0 cells and cells in the G2/M phase of the cell cycle).
Subject(s)
HL-60 Cells/drug effects , HL-60 Cells/radiation effects , Paclitaxel/pharmacology , Radiation-Sensitizing Agents , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Cell Survival/drug effects , Cell Survival/radiation effects , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Humans , Leukemia, Myeloid/drug therapy , Leukemia, Myeloid/radiotherapyABSTRACT
The radioprotective activity of eight selected copper (II) carboxylates--Cu (RCOO)2.nL (R = alkyl, aryl, 2-furyl and 2-thienyl; L usually represents water)--was assayed in a model of lethally gamma-irradiated (9 Gy, 0.97 Gy/min) mice. The compounds tested were applied (as solutions in saline) s.c. in three single doses of 20 mumol/kg 48.24 and 6 h before irradiation. The highest radioprotective effects were measured by survival of mice achieved after premedication of animals with copper (II) 2-thenoate monohydrate (77%), copper (II) acetylsalicylate (64%), copper (II) 2-methoxybenzoate monohydrate (62%) and copper (II) acetate monohydrate (54%). On the other hand, survival of vehicle-pretreated mice was only 10%. The observed biological properties of complexes are discussed in relation to their structures.
Subject(s)
Radiation-Protective Agents , Animals , Copper/administration & dosage , Gamma Rays , Guinea Pigs , Mice , Mice, Inbred ICR , Organometallic Compounds/administration & dosage , Radiation-Protective Agents/administration & dosageABSTRACT
The passage of 6 model drugs; acetylsalicylic acid, chloramphenicol, ethimizol, carbisocaine, heptacaine, and diazepam, through the blood-brain barrier, was determined in unirradiated control rats and in animals 1, 3, and 7 days after irradiation of the head only with a dose of 25 Gy from a 60Co source. The brain uptake index (BUI), which compares the uptake of the test substance with that of 3H2O 5 s after their injection into the common carotid artery, was significantly increased in comparison with unirradiated controls 7 days after irradiation, for all substances tested except for ethimizol. For acetylsalicylic acid and chloramphenicol it was also significantly increased in the other time intervals. The less lipophilic substances showed a greater relative increase of BUI than the more lipophilic ones.
Subject(s)
Blood-Brain Barrier/radiation effects , Cranial Irradiation , Animals , Aspirin/pharmacokinetics , Brain/metabolism , Carbamates/pharmacokinetics , Chloramphenicol/pharmacokinetics , Cobalt Radioisotopes , Diazepam/pharmacokinetics , Etimizol/pharmacokinetics , Male , Piperidines/pharmacokinetics , Rats , Rats, Inbred Strains , Regression AnalysisSubject(s)
Etimizol/blood , Imidazoles/blood , Animals , Cobalt Radioisotopes , Dose-Response Relationship, Radiation , Gamma Rays , Kinetics , Male , Rats , Rats, Inbred StrainsABSTRACT
Decreased clearance of i.v. or intratracheally administered gentamicin was observed in rats following single whole-body irradiation. 6 Gy 60Co. reaching its lowest rate on the 7th post-irradiation day. Simultaneously the absorption rate of gentamicin from the lungs was found to be increased.
