Changes in DNA capacity for actinomycin-D binding in nuclei of interphase cells.

3H-AMD binding to DNA in interphase nuclei was tested on asynchronous and synchronous LS/BL cell populations under physiological conditions and after exposure to gamma rays (60Co). 3H-AMD binding to DNA in an asynchronous cell population appeared to be nearly constant and independent of 3H-AMD concentration. However, in comparing individual cells, a great variability could be observed. In synchronized cells the DNA accessibility for 3H-AMD binding changed in the course of the cell cycle, with a maximum occurring at the late G1-phase (13.95 X 10(-12) mumol/nucleus) and a minimum at the late G2-phase (2.63 X 10(-12) mumol/nucleus). In irradiated cells the DNA capacity for 3H-AMD binding was growing with the increasing dose (5-80 Gy) from 4.9 to 11.2 X 10(-12) mumol 3H-AMD/nucleus.

The rates of replicative and unscheduled DNA synthesis as functions of temperature in LS/B1, L-As and L-C3 cells.

The relative rates of replicative and unscheduled DNA synthesis were determined over a temperature range of 2 degrees to 42 degrees C in LS/B1, L-As and L-C3 cells. The rates were determined by measuring the amount of 3H-dTh incorporated into DNA during 60 min incubation of cells at a given temperature. Acid-resistant 3H-activity incorporated into DNA at 2 degrees C was evaluated as evidence of DNA turnover, not non-specific adsorption of 3H-dTh. The relative rates of RDS and UDS were expressed as functions of temperature and from the data the values of Q10 and Eact necessary for incorporation of one mole of dTh into DNA during RDS and UDS were calculated. The values of Q10 and Eact are comparable to those reported for HeLa, V-79, L5/78Y and the epithelial cells. The experimentally determined values of Q10 and Eact for UDS in the lines tested did not vary. UDS, compared to RDS, is evaluated as a process with lesser demands for energy.

Inhibition of entry into S phase and DNA synthesis in bone marrow cells of mice by repeated injections of gentamycin.

The effect of gentamycin on bone marrow cells in unirradiated and irradiated mice was investigated by 3H-dTh incorporation into DNA using microautoradiography. Gentamycin was injected in vivo at 20 mg base/kg body weight at 8-h intervals during three days. In mice exposed to 4.78 Gy the injections of gentamycin were started on the 7th day after irradiation. In granulopoietic and erythropoietic cells the inhibition of entry of cells into S phase and the retardation of DNA replication was about 20%. The roughly 30% inhibition of entry of cells into S phase observed when the bone marrow cell population has been evaluated as a whole is discussed in terms of increased sensitivity of the young blast-like cells.

The effect of chloramphenicol on erythropoiesis in X-irradiated mice.

Mice irradiated with a dose of 4,78 Gy X-radiation were treated 3 or 5 days with a thrice-daily dose of chloramphenicol of 160 or 320 mg/kg. Observation of the incorporation of 59Fe into the heme fraction suggested that chloramphenicol has a depressive effect on erythropoiesis in the spleen of nonirradiated animals, and clearly proved this in irradiated ones. Depression in the bone marrow of nonirradiated animals was not observed, in irradiated animals a depressive effect was shown, though less strong than in the spleen. As benefits these findings there is an accentuation of postirradiational anemia after chloramphenicol treatment of irradiated animals, and signs of incipient anemia in nonirradiated animals. All the effects mentioned were repaired within 14 days of the end of chloramphenicol treatment.

Chloramphenicol toxicity in radiation disease.

The effect of chloramphenicol given in high therapeutic doses, in the course of postirradiation syndrome in irradiated mice of C57Bl/10 strain, is reported. Chloramphenicol treatment increased postirradiation mortality of animals and intensified suppression of the proliferating and differentiating processes in hemopoietic organs of the irradiated animals. The results support the assumption that postirradiation depression of hemopoiesis is a contraindication to the therapeutic employment of this antibiotic.

Inhibition of bone marrow cell proliferation and DNA replication induced by chloramphenicol.

The effect of CAP on proliferations of bone marow cells from unirradiated and irradiated (4.78 Gy) C57BL/10 mice was investigated by 3H-dTh incorporation into DNA of individual cells using autoradiography. CAP was administered from day 7 to day 10 after irradiation. CAP decreases the rate of entry of cells into S phase and the rate of 3H-dTh incorporation into DNA during replication. Cells of the erythropoietic series are mainly involved in this decrease. CAP has roughly the same inhibitory effect on unirradiated and irradiated cell populations.