Leukemic Cell DNA Research Articles

Differences Between the Integration of Avian Myeloblastosis Virus DNA in Leukemic Cells and of Endogenous Viral DNA in Normal Chicken Cells

The nature of integrated viral DNA in normal and leukemic chicken cells has been studied by sequential nucleic acid hybridization procedures that localize the viral specific DNA in cellular DNA regions differing in reiteration frequency. First, DNA.DNA reassociation was employed to fractionate cellular DNA sequences according to their reiteration frequencies. Next, the DNA in each fraction was denatured, immobilized on nitrocellulose filters, and then hybridized with viral [(3)H]RNA. In normal cells, endogenous viral DNA appears to be associated with cell sequences reiterated 1200 times, and each integration unit appears to have a maximal size approximately equivalent to the 35S RNA subunit of the virion. In infected cells, additional viral sequences are found which reassociate as if they integrated adjacent to unique cellular DNA, or in tandem with endogenous viral DNA.

Endogenous Guinea Pig Virus: Equability of Virus-Specific DNA in Normal, Leukemic, and Virus-Producing Cells

The kinetics of hybrid formation between the RNA of BrdU-activated endogenous guinea pig virus and the DNA of leukemic, normal, or BrdU-activated guinea pig cells were measured by the technique of RNA.DNA hybridization in DNA excess. The results suggest that virus-specific sequences representing some 60-70% of the viral genome are unique (2-3 copies per haploid cell genome), while the remainder (30-40%) are reiterated (147 copies), and that the reiterated virus-specific DNA may be composed of more than one species, each having a different reiteration frequency. No difference was found in the quantity of viral DNA sequences contained in normal, leukemic, or bromodeoxyuridine-activated guinea pig cells. These data are considerably different from those reported for exogenous (infectious) oncornaviruses, where cells infected or transformed by exogenous RNA tumor viruses have been shown to contain increased amounts of virus-specific DNA. The data reported here are consistent with the contention that preexisting viral genes are activated by bromodeoxyuridine treatment. Results of hybridization experiments done at different DNA/RNA ratios suggest that although the virus-specific DNA is partly unique and partly reiterated, the viral RNA does not contain any detectable internal reiteration. Total mass of the viral RNA sequences is around 0.7 to 1 x 10(7) daltons.

Leukemia-specific DNA sequences in leukocytes of the leukemic member of identical twins.

The discovery in human leukemic cells of particulate elements encapsulating 70S RNA and RNA-directed DNA polymerase made possible the synthesis of a [(3)H]DNA probe that could detect leukemia-specific sequences in the DNA of normal and leukemic individuals. In an earlier study of a series of unrelated leukemic patients, we established that the nuclear DNA of their leukemic cells contain particle-related sequences that cannot be detected in leukocytes of normal individuals. This result is inconsistent with the virogene concept that demands the inclusion of one complete copy of oncogenic information in the genome of every normal cell. The present study carries this analysis one step further by showing, with two sets of identical twins, that the leukemic member contains particle-related sequences in the DNA of his leukocytes that cannot be detected in the leukocytes of his healthy identical sibling. This finding implies that the additional leukemia-specific information found in the DNA of the leukemic individuals must have been inserted subsequent to fertilization. This outcome argues against the virogene hypothesis or any other etiologic concept that invokes vertical transmission through the germ line of the particle-related information found uniquely in the DNA of leukemic cells.

In vitro effect of sodium warfarin on DNA and RNA synthesis of mouse L1210 leukemic cells and Walker tumor cells.

Medical imaging that uses ionizing radiation, such as CT, radiography, nuclear medicine, and fluoroscopy, is a cornerstone of the care of oncology patients and provides great benefit. Ionizing radiation at high doses is a known carcinogen.The exact degree of the risk of carcinogenesis from the lower doses of ionizing radiation used in medical imaging is less clear. The purpose of this review is to provide the oncology community with knowledge about the doses used in medical imaging, radiation-induced cancer risks from imaging, considerations to keep in mind when balancing imaging benefits and risks in pediatric and adult oncologic settings, dose reduction strategies, and the "Image Gently" and "Image Wisely" campaigns; the latter campaigns facilitate the translation of existing evidence into best practices for providers and patients.

Inhibition of repair of DNA single strand breaks in mouse leukemia cells by Actinomycin D

The effects of Actinomycin D, cytosine arabinoside and temperature shifts on the repair of single strand breaks produced in murine leukemia cell DNA by ionizing radiation have been studied. A recently introduced modification of the alkaline sucrose sedimentation methods was used, allowing breaks to be demonstrated following clinical range irradiation doses. The results contrast to previous data using standard gradient procedures and indicate that low concentrations of Actinomycin D can inhibit single strand break repair, while cytosine arabinoside is ineffective. Inhibition can also be demonstrated by temperature shifts to 3° but not 24°, paralleling previous results from cellular repair studies (Elkind-Sutton repair). The results are consistent with the hypothesis that the accumulation of sublethal radiation damage in mammalian cells may be based on residual non-repaired single strand breaks.

DNA complementary to viral RNA in leukemic cells induced by avian myeloblastosis virus.

Nucleic acid hybridization studies were made between 71S-AMV-RNA and DNA from leukemic myeloblasts and from normal chicken cells. There was homology between the viral RNA and chicken cell DNA and to a greater extent between viral RNA and leukemic cell DNA. Leukemic cell DNA hybridized approximately twice as much viral RNA as did normal chicken DNA. Thermal melting studies showed that the viral RNA bound to normal and leukemic cell DNA consists of long polynucleotides (T(m) = 87 degrees and 92 degrees C, respectively, in 2x saline citrate). This suggests that the leukemic cells contain a DNA template of the viral RNA.

Complex mitochondrial DNA in leukemic and normal human myeloid cells.

Mitochondrial DNA's from the peripheral blood of 14 patients with granulocytic leukemia contained a circular dimer form. No such structure could be found in M DNA's from three patients with nonmalignant proliferations of granulocytes. The frequency of the circular dimer form is reduced upon treatment with antileukemic drugs. The above results suggest that a significant relation exists between the formation and presence of the circular dimer M DNA form and granulocytic leukemia in man.

Interaction of mouse leukemic cells with L cells in tissue culture: I. Passage of leukemic cell DNA into the nuclei of L cells

3H-thymidine-labeled mouse leukemic cells were cultivated together with L cells for 1, 2, 3, and 5 days in the presence of excess carrier thymidine. Coverslips with adherent monolayers of L cells and leukemic cells were fixed and subjected to autoradiogaphy. The resulting autoradiographic images were controlled by means of repeated autoradiography and DNase digestion. A great proportion of leukemic cells was phagocytized and digested inside the cytoplasmic vacuoles of L cells. Pycnotic cells which failed to come in contact with L cells usually formed an extracellular corona of DNase-sensitive radioactivity. A definite amount of DNase-sensitive label was found in L cells. It was randomly distributed in the cytoplasm and, on the other hand in the nucleolus-associated chromatin. Since no appreciable amount of cytoplasmic as well as nucleolar label was removed by DNase action on living cells, the possibility was excluded that labeled DNA was adsorbed on the L cell surface. About 0.6 to 1.9 per cent of L cells contained labeled DNA in one or several nucleolar regions of the nucleus after 24 h of incubation; the percentage slowly declined in the course of longer incubation periods. Control experiments replacing tritium radioactivity of leukemic cell DNA by that of 3H-thymidine under otherwise identical experimental conditons gave evidence that labeling was not associated with DNA synthesis in L cells. The observations are explained in terms of DNA translocation from donor leukemic cells into recipient L cells. A rough estimate indicates that the amount of incorporated DNA represents 4.8 per cent of the mean DNA content of L cell nucleus.

Cytochemical population analyses of the DNA, RNA and protein content of human leukemic cells.

Cytochemical population analyses of the DNA, RNA and protein content of human leukemic cells.

Cell proliferation in leukemia during relapse and remission. I. DNA and RNA synthesis of leukemic cells in the bone marrow in vitro.

Cell proliferation in leukemia during relapse and remission. I. DNA and RNA synthesis of leukemic cells in the bone marrow in vitro.

LEUKEMIC CELL PROLIFERATION AS DETERMINED BY IN VITRO DEOXYRIBONUCLEIC ACID SYNTHESIS*

The immature cells circulating in the blood of leukemic patients are believed to reflect the proliferative activity of the malignant tissue. The rate of DNA synthesis by these cells may provide information as to the rate of growth of leukemic cells, since the DNA synthetic period is believed to occupy a specific interval in the generation cycle of dividing cells. This report gives our findings concerning this parameter of leukemic proliferation, as reflected by the uptake of isotopes into leukemic cell DNA in vitro. The results indicate that the conceptualization of the acute leukemic process, as one involving rapid cell growth, must be viewed in the perspective of the total bulk of divisible cells,