ABSTRACT
Murine leukemic lymphoblasts L5178Y-R (LY-R) undergo conversion into their L5178Y-S (LY-S) variant as a result of prolonged (5 months to 4 years) cultivation in vitro. LY-R cells are highly tumorigenic in DBA/2 mice; resistant to X-rays [D0 (mean lethal dose [reciprocal of the slope of the linear portion of dose-survival curve] ) = 0.91 grays]; and sensitive to ultraviolet radiation (D0 = 0.7 J/sq m), short (up to 60 min) heat (43 degrees) treatment, and certain potential cancer drugs. LY-S cells are practically nontumorigenic in DBA/2 mice; sensitive to X-rays (D0 = 0.56 grays); and resistant to ultraviolet radiation (D0 = 5.5 J/sq m), short heat treatment, and the drugs. The differences in sensitivity of these two cell strains to physical and chemical agents are paralleled by differences in DNA repair efficiency. Although both strains can be cloned in soft agar, LY-S cells invariably show higher plating efficiencies. In vitro mean doubling times are 12 to 15 hr and approximately 10 hr for LY-R and LY-S cells, respectively. The actual loss of tumorigenicity and changes in radio- and photosensitivity associated with conversion of LY-R cells into LY-S cells occur within a short time. This indicates that these changes (and probably other phenotypic changes mentioned above) result from a single event or from several events occurring within a relatively short time elicited by in vitro culture conditions.
Subject(s)
Leukemia L5178/pathology , Leukemia, Experimental/pathology , Animals , Cell Survival/radiation effects , Cells, Cultured , Mice , Neoplasm Transplantation , Photic Stimulation , Time Factors , Ultraviolet RaysABSTRACT
Combination of lidocaine (6 mg/ml) and X-rays was used for treatment of two strains of L5178Y lymphoma cells under hypoxic conditions. The strains L5178Y-S (radiosensitive) and L5178Y-R (radioresistant) differ in radiosensitivity by a factor of about 1.4 whereas they are equally sensitive to lidocaine. For combined treatment of L5178Y-R cells the enhancement ratio was 1.4 and for that of L5178Y-S cells 1.0. Cell partition between two aqueous polymer phases [Dextran T500 and poly(ethylene glycol) 6000] does reflect neither viability nor the commitment of treated cells to interphase or reproductive death.
Subject(s)
Cell Survival/drug effects , Lidocaine/pharmacology , Lymphoma/pathology , Radiation Tolerance , Cell Survival/radiation effects , Cells, Cultured , Humans , OxygenABSTRACT
Effects of treatment with misonidazole under aerobic conditions were examined in L5178Y-R and L5178Y-S cells. These cells slightly differ in susceptibility to the drug, however, the effects of treatment are similar: 1. slowing down growth without affecting viability at low doses; 2. cell lethality at higher doses with rapid elimination of dead cells from the population and resuming normal growth; 3. decrease in 3H-thymidine incorporation. These effects of misonidazole were strikingly similar to those of antimycin A (1 microgram/ml) and KCN (1 mM). It seems that the common cause of the described manifestations of cellular damage inflicted by all three chemicals is energy depletion due to disturbances in the function of mitochondrial electron transport.
Subject(s)
Antimycin A/pharmacology , Cyanides/pharmacology , Leukemia L5178/metabolism , Leukemia, Experimental/metabolism , Misonidazole/pharmacology , Nitroimidazoles/pharmacology , Potassium Cyanide/pharmacology , Aerobiosis , Animals , Cell Division/drug effects , Cell Line , Cell Survival/drug effects , DNA, Neoplasm/biosynthesis , MiceABSTRACT
Murine leukaemic lymphoblasts L5178Y-S were exposed to: (a) 104 muCi of 3HOH for time intervals from 25 to 600 h, (b) 10 muCi of L-[4,5(n)-3H] lysine for 25 to 600 h, and (c) 0.05 muCi of [methyl-3H]thymidine for 4 to 600 h. Extended post-exposure observations of growth disturbances and viability changes indicate marked differences between heritable lesions induced by the three tritiated compounds. After exposures to tritiated lysine and tritiated water, the damage was predominantly of non-lethal character while in the populations previously exposed to tritiated thymidine most of the cells eliminated during the post-exposure growth were lethally damaged. In all cases examined growth retardation was observed followed by growth at the normal rate. An exception concerned a cell culture exposed for 600 h to tritiated thymidine for which the slowed-down growth was observed for ca seventy cell generations.
Subject(s)
Lymphoma , Tritium , Animals , Cell Survival/radiation effects , Cells, Cultured , Leukemia, Experimental/pathology , Lymphoma/pathology , Lysine , Mice , Radiation Dosage , Thymidine , Tritium/adverse effects , X-RaysABSTRACT
Two strains of murine leukaemic lymphoblasts: L5178Y-R and L5178Y-S differing in the X-ray sensitivity by a factor of ca. 2 and showing X-ray-UV-light cross-sensitivity were exposed to: (a) 104 muCi/ml of HTO for time intervals from 25 to 600 h, (b) 10 muCi/ml of L-[4,5(n)-3H]lysine for 25 to 600 h, and (c) 0.05 muCi/ml of [methyl-3H] thymidine for 4 to 600 h. After completion of the exposure, survival was determined by cloning or by backward extrapolation of growth curves. In the case of HTO and 3H-thymidine exposure time the survival relationship passed through broad minima (75--200 and 50--400 h for (a) and (c), respectively). After longer exposures, higher survivals were observed reaching values close to 1 in the extreme cases. The results of shorter exposures indicate that L5178Y-R and L5178Y-S cells considerably differ in their susceptibilities to the tritiated compounds and that this difference increases with the shift of 3H localization towards DNA.
