Suppression of the initiation of DNA synthesis as an index of cellular radiosensitivity

A gamma-radiation dose (Di) suppressing DNA synthesis initiation by 35% in primary suspension cultures of mammalian cells, is nearly the same as D0 for survival of clonogenic cells of the same lines and tissues. The extent of DNA synthesis suppression is assessed by impulse 3H-thymidine incorporation in the acid-insoluble fraction of irradiated cells. The values of Di determined in this way for HeLa cells, Ehrlich ascites tumor cells, mouse bone marrow and thymus cells are 2.0, 1.5, 1.5, and 1.0 Gy, respectively; as determined by clonogenic capacity of these cells, Di = 1.9, 2.0, 1.3, and 1.0 Gy, respectively.     

The effect of irradiation on the growth of human laryngeal tumors transplanted under the kidney capsule of immunocompetent mice

A study was made of the influence of gamma-radiation on the growth of human larynx squamous cell carcinoma transplanted under the capsule of the kidney of immunocompetent mice. The transplants were shown to increase in size 6 days after transplantation. Irradiation of animals 24 h after transplantation inhibited considerably the tumor growth. However, the preirradiation (24 h before operation) inhibited the growth of nonirradiated transplants to the same extent as the exposure of mice with the transplanted tumor fragments did: the radiation dose that induced 50% inhibition of the growth was 4.5 Gy and 5.3 Gy, respectively. Preliminary data indicate that tumor fragment of patients with the unfavourable prognosis increase in size and respond to radiation to a lesser extent.     

DNA replication in mammalian cells after the action of physical, chemical or biological factors. VI. The recovery of DNA synthesis in a culture of irradiated cells

The kinetics of DNA synthesis restoration in cultured HeLa cells and in L-929 mouse fibroblasts irradiated by gamma-rays of 60Co with a dose of 10 Gy was studied. Early after irradiation the rate of DNA synthesis in HeLa cells measured with 3H-thymidine incorporation was seen to decrease. Two hours later the incorporation starts to increase to reach the control level 4 hours after irradiation and then becomes even higher than this level. The distribution of cells among phases of the cell cycle measured with flow cytometry undergoes changes. 4-6 hours after irradiation part of S-phase cells increased contributing presumably to the elevating of 3H-thymidine incorporation observed at this time. The restoration of the incorporation was suppressed by inhibitors of protein and RNA synthesis--cycloheximide and actinomycin D. It is suggested that the processes of restoration of DNA synthesis in irradiated cells can be of inducible nature. In irradiated HeLa and L-929 cells the restoration of DNA synthesis is resistant to novobiocin, an inhibitor of DNA replication.     

5-fluorodeoxyuridine induces radioresistant synthesis of DNA and sensitizes HeLa cells to gamma radiation

It was shown that preincubation of HeLa cells with 5-fluorodeoxyuridine (10(-6) M) induced DNA synthesis resistant to gamma-radiation (6 Gy). At the same time, the death rate of exposed cells increased and nucleoid relaxation decreased. The role of DNA synthesis inhibitors in the reproductive death of exposed cells is discussed.     

Mechanism of the cytotoxic action of formaldehyde on cultured mammalian cells

Induction and repair of DNA lesions cell inactivation and repair of potentially lethal damages (PLD) were studied after the treatment of cultured cells with formaldehyde. Formaldehyde induced the appearance of a rapidly sedimentating DNA--membrane complex. This complex may contain up to 50% of choline and no more than 3-5% of leucine or lysine incorporated in the acid insoluble cell fraction, Inhibition of DNA synthesis, induction of single strand DNA breaks and/or alkali-labile sites increased with the raise of formaldehyde concentration. A good correlation is observed between with the raise of formaldehyde concentration. A good correlation is observed between with the raise of formaldehyde concentration. A good correlation is observed between the increasing DNA quantities in the rapid sedimentation complex and the cell lethality.     

Latent autoantibodies to cardiolipin in the blood serum of healthy subjects

Pooled health blood donors' sera were fractionated by gel filtration and/or ion exchange chromatography on strong anion-exchanger. Measurement of anticardiolipin antibodies levels by ELISA method shows that gel filtration at pH 4.05 and 9.2 (complex-degradation conditions) leads to increase in summary levels while after elution at neutral pH such an effect did not appear. Light increasing of anticardiolipin levels was also noted after fractionation on QAE-Sephadex. Data obtained state that anticardiolipin autoantibodies amount in sera is greater than it can be detected by direct measurement in untreated serum samples. Existence of "hidden" anticardiolipin autoantibodies supposes the hypothesis about alternative way of humoral immunity regulation by blocking anti-self antigens activities with serum biopolymers.     

Pre-steady state kinetics of the ferroxidase reaction catalyzed by ceruloplasmin

Analysis of the presteady-state step of the ferroxidase reaction catalyzed by ceruloplasmin revealed that the kinetic curve for the reaction product accumulation versus time is characterized by an induction period, tau, whose value does not change within the pH range of 5.0-7.5. The value of tau decreases with a rise in the enzyme concentration and increases with a rise in the substrate concentration at constant Fe(II) and E0 concentrations. A reaction scheme is proposed which points to the existence of an induction period in the ceruloplasmin-catalyzed ferroxidase reaction. It was shown that the calculated values of tau = f([Fe(II)]0) and tau = f([E]0) obtained through the use of differential equations qualitatively coincide with the corresponding experimental values.     

Arthropod toxins inhibiting Ca2+ and Na+ channels prevent AC‐1001 H3 peptide‐induced apoptosis

Peptide toxins of arthropods are one of the potential sources of bioactive substances. Toxins are able to bind to calcium channels and block them. Ca²⁺ ions play an important role in many cell processes, in particular, in apoptosis. In this work, we study the effect of some arthropod toxins on intracellular processes associated with the induction of apoptosis. Synthetic analogs of U₅‐scytotoxin‐Sth1a, ω‐hexatoxin‐Hv1a, ω‐theraphotoxin‐Hhn2a, and μ‐agatoxin‐Aa1a toxins—inhibitors of calcium L, P, and Q channels and sodium channels were used in the study. Apoptosis was induced by AC‐1001 H3 peptide. We study the effect of toxins on the level of apoptosis, ROS, mitochondrial potential, GSH, and ATP in CHO‐K1 cells. We show that all the tested toxins are able to dose dependently block the induction of apoptosis triggered by AC‐1001 H3 and reduce the level of natural apoptosis in CHO‐K1 cells. Cell incubation with apoptosis inducer AC‐1001 H3 in the presence and absence of toxins causes an increase in the intracellular concentrations of ROS, ATP, and mitochondrial potential and decreases the GSH concentration. The present study reveals the antiapoptotic effect of a number of arthropod peptide toxins. The toxins studied can represent a novel approach used in the treatment of pathologies associated with the activation of apoptotic mechanisms.     

Conserved intron positions in ancient protein modules

Background  

The timing of the origin of introns is of crucial importance for an understanding of early genome architecture. The Exon theory of genes proposed a role for introns in the formation of multi-exon proteins by exon shuffling and predicts the presence of conserved splice sites in ancient genes. In this study, large-scale analysis of potential conserved splice sites was performed using an intron-exon database (ExInt) derived from GenBank.     

Childhood leukemia in Ukraine after the Chornobyl accident

Radiation and Environmental Biophysics - This population-based ecological study analyzes the prevalence of childhood leukemia in Ukraine before and after the Chornobyl nuclear power plant accident,...