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Biomedical subjects

R B Painter

Publications and source records attributed to R B Painter.

At least 37 records · Page 2Linked to original sources
PubMed1985

3-Aminobenzamide does not affect radiation-induced inhibition of DNA synthesis in human cells.

3-Aminobenzamide (3AB), a potent inhibitor of poly(ADP-ribose) synthesis, does not affect the dose response for ionizing radiation-induced inhibition of DNA synthesis in human fibroblasts. If the radioresistant DNA synthesis observed in fibroblasts from patients with ataxia-telangiectasia (A-T) were due to reduced poly(ADP-ribose) synthesis after irradiation, as has been proposed, the response in normal cells incubated with 3AB would have been similar to that observed in A-T cells. Therefore, altered poly(ADP-ribose) synthesis in A-T cells is not solely responsible for their radioresistant DNA synthesis.

Ataxia Telangiectasia↗
PubMed1985

Complementation analysis of ataxia-telangiectasia.

In a number of laboratories genetic analysis of ataxia-telangiectasia (AT) has been performed by studying the expression of the AT phenotype in fused somatic cells or mixtures of cell-free extracts from different patients. Complementation of the defective response to ionizing radiation was observed frequently, considering four different parameters for radiosensitivity in AT. The combined results from studies on cultured fibroblasts or lymphoblastoid cells from 17 unrelated families revealed the presence of at least four and possibly nine complementation groups. These findings suggest that there is an extensive genetic heterogeneity in AT. More extensive studies are needed for an integration of these data and to provide a set of genetically characterized cell strains for future research of the AT genetic defect.

Ataxia Telangiectasia↗
PubMed1985

Altered DNA synthesis in irradiated and unirradiated ataxia-telangiectasia cells.

DNA synthesis in cells from ataxia-telangiectasia (AT) patients differs from that in normal cells in two principal ways. In unirradiated cultures, AT cells have a lower inherent rate of DNA synthesis (and, therefore, a longer S phase) than normal cells and, in cultures exposed to ionizing radiation, DNA synthesis is not inhibited as it is in normal cells; this radioresistant DNA synthesis is due to completely resistant DNA chain elongation and partially resistant DNA replicon initiation. It is probable that the defects in DNA synthesis in irradiated and unirradiated cells are related and are at least partially involved in the pathogenesis of this syndrome.

Ataxia Telangiectasia↗
PubMed1983

Altered protein synthesis in ataxia--telangiectasia fibroblasts.

Analysis of protein production in various strains of ataxia--telangiectasia (A--T) fibroblasts demonstrated the overproduction of a group of secreted proteins and variations in the protein characteristics of the extracellular matrix. The most prominent differences involved fibronectin, which was identified by immunochemical analysis. One- and two-dimensional gel electrophoresis demonstrated differences in the production, accumulation, and molecular weight of fibronectin on the cell surface and in the culture medium as compared to normal human fibroblasts. Three other secreted proteins with molecular weights of 185 000, 150 000, and 70 000 were also observed to be produced in excess amounts in some strains of A-T. The finding that extracellular matrix alterations are involved in the abnormal DNA synthesis and reduced cell survival in A-T cells in response to X radiation would be additional evidence for a close association between the extracellular and nuclear architecture.

Ataxia Telangiectasia↗
PubMed1983

Are lesions induced by ionizing radiation direct blocks to DNA chain elongation?

Ionizing radiation blocks DNA chain elongation in normal diploid fibroblasts but not in fibroblasts from patients with ataxia-telangiectasia, even though there are no differences in the damage induced between the two cell types. This difference suggests that radiation-induced lesions in DNA are not themselves blocks to chain elongation in ataxia cells and raises the possibility that in normal cells a mediator exists between DNA damage and chain termination.

Ataxia Telangiectasia↗
PubMed1982

The Hela DNA-synthesis inhibition test as a rapid screen for mutagenic carcinogens.

90 agents have been tested in the HeLa DNA-synthesis inhibition test. This test detects strong mutagens and carcinogens except when difficulties with metabolic activation are encountered. Weaker DNA-damaging agents are generally positive in the test but require relatively high concentrations (greater than 1 mM). Very weak agents, such as saccharin, are not positive. Only 1 false positive has been encountered and the dose response for it (cytochalasin B) is atypical. The test does not seem suitable for complex mixtures, probably because ingredients that do not damage DNA but inhibit DNA synthesis by another mechanism can mask the action of a DNA-damaging agent. Inhibition of DNA synthesis in HeLa and other mammalian cells is best used as a rapid and inexpensive screening procedure to detect relatively strong mutagenic carcinogens.

Carcinogens↗
PubMed1982

DNA repair assays as tests for environmental mutagens. A report of the U.S. EPA Gene-Tox Program.

A literature review was undertaken to determine the usefulness of DNA repair assays, other than unscheduled DNA synthesis, as screening techniques for mutagenic carcinogens. 92 reports were found to contain useful data for 49 chemicals using 6 techniques, namely, (1) cesium chloride equilibrium density gradients to study repair replication, (2) benzoylated naphthoylated diethylaminoethyl cellulose columns to study repair replication, (3) 313-nm irradiation of DNA containing bromodeoxyuridine to study repair replication, (4) alkaline elution to study repair of single-strand breaks and crosslinks, (5) alkaline sucrose gradients to study repair of single-strand breaks, and (6) direct assays for removal of adducts from DNA. Almost all of the 49 chemicals studied were known mutagens or carcinogens and/or known inducers of DNA repair, 9 compounds failed to elicit DNA repair by at least 1 assay technique, and at least 3 of these were not tested by the most appropriate and sensitive method. Nevertheless, although valid for studying repair phenomena in eukaryotic cells, these assays are not considered useful for screening. They are time-consuming, expensive, and/or require highly specialized skills. Despite the high frequency of positive reports, it is obvious from the literature that repair assays will fail to detect, or will detect with low efficiency, those agents whose main action is either intercalation or induction of strand breaks. For these and other reasons, DNA repair as a basis for screening for mutagenic carcinogens is not considered to be a useful concept.

Bromodeoxyuridine↗
PubMed1982

Complementation of the defects of DNA synthesis in irradiated and unirradiated ataxia-telangiectasia cells.

Mutant subtypes in the human genetic disease ataxia-telangiectasia (A-T) were classified by means of an assay system that monitors complementation of defects in DNA synthesis. Anomalies in DNA synthesis have been observed previously in A-T cells, both in their failure to inhibit DNA synthesis immediately after exposure to ionizing radiation and in their prolonged S phase. Polyethylene glycol-mediated cell fusion and autoradiography were combined with selective identification of different A-T cell populations by fluorescent colored microspheres to determine complementation capabilities of various A-T cell combinations. Five complementation groups were identified by both a 30-40% increase in the rate of DNA synthesis in unirradiated heterokaryons and the appearance of normal inhibition of DNA synthesis after x-irradiation of heterokaryons. The correlation observed between these phenomena suggests that the defects in A-T cells involve problems in initiation of DNA synthesis.

Ataxia Telangiectasia↗
PubMed1982

Structural changes in chromatin as the basis for radiosensitivity in ataxia telangiectasia.

Cells from patients with the autosomal recessive genetic disease ataxia telangiectasia (AT) are more sensitive to killing by ionizing radiation than are cells from normal individuals. In contrast, ionizing radiation inhibits the rate of DNA synthesis much less in AT cells than in normal cells. This radioresistant DNA synthesis can be partly mimicked by treating normal cells with caffeine or by incubating normal cells in hypertonic medium after irradiation. Because both of these treatments seem to affect chromatin structure, it is possible that the radioresistant DNA synthesis in AT cells is due to an intrinsic difference in chromatin structure between AT cells and normal cells. This difference allows normal cells to recognize chromatin damage and to pause and repair it, whereas AT cells fail to recognize this damage, which leads to chromosomal aberrations.

Ataxia Telangiectasia↗
PubMed1981

DNA fork displacement rates in human cells.

DNA fork displacement rates were measured in 20 human cell lines by a bromodeoxyuridine-313 nm photolysis technique. Cell lines included representatives of normal diploid, Fanconi's anemia, ataxia telangiectases, xeroderma pigmentosum, trisomy-21 and several transformed lines. The average value for all the cell lines was 0.53 0.08 mum/min. The average value for individual cell lines, however, displayed a 30% variation. Less than 10% of variation in the fork displacement rate appears to be due to the experimental technique; the remainder is probably due to true variation among the cell types and to culture conditions.

Ataxia Telangiectasia↗