Diversity of prion strains was attributed to an elusive nucleic acid, yet a search spanning nearly two decades has failed to identify a prion-specific polynucleotide. In our search for a prion-specific nucleic acid, we analyzed nucleic acids in purified fractions from the brains of Syrian hamsters infected with Sc237 prions. Purification of Sc237 prions removed nucleic acids larger than 50 nucleotides as measured by return refocusing electrophoresis (RRGE). To determine the size of the largest polynucleotide present in purified fractions at an abundance of one molecule per infectious (ID50) unit, we measured prions present after inoculation. In order to account for the rapid clearance of prions after intracerebral inoculation, we determined the number of PrP(Sc) molecules and ID50 units of prions that were retained in brain. Factoring in clearance after inoculation, we estimate that the largest polynucleotide present in our purified fractions at one molecule per ID50 unit is approximately 25 nucleotides in length. In the same fractions, there were approximately 3,000 protease-resistant PrP(Sc) molecules per ID50 unit after accounting for clearance of PrP(Sc) following inoculation. We compared the resistance of Sc237 and 139H prions to inactivation by UV irradiation at 254 nm. Irradiation of homogenates and microsomes diminished prion infectivity by a factor of approximately 1,000 but did not alter the strain-specified properties of the Sc237 and 139H prions. The data reported here combined with the production of synthetic prions argue that the 25-mer polynucleotides found in purified prion preparations are likely to be host encoded and of variable sequence; additionally, these 25-mers are unlikely to be prion specific.

Following more than a decade of scientific debate about the setting of a standard for 222Rn in drinking water, Congress established a timetable for the promulgation of a standard in the 1996 Amendments to the Safe Drinking Water Act. As a result of those Amendments, the EPA contracted with the National Academy of Sciences to undertake a risk assessment for exposure to radon in drinking water. In addition, the resulting committee was asked to address several other scientific issues including the national average ambient 222Rn concentration and the increment of 222Rn to the indoor-air concentration arising from the use of drinking water in a home. A new dosimetric analysis of the cancer risk to the stomach from ingestion was performed. The recently reported risk estimates developed by the BEIR VI Committee for inhalation of radon decay products were adopted. Because the 1996 Amendments permit states to develop programs in which mitigation of air-producing health-rsik reductions equivalent to that which woul...

3-Aminobenzamide (3AB) is widely used as an inhibitor of poly(ADP-ribose) synthetase to study the effect of protein ribosylation on various cellular processes, but the specificity of its inhibition has not been demonstrated. We found that 3AB has a wide range of effects on DNA precursor metabolism, as determined by high-performance liquid chromatographic separation of deoxynucleosides derived from enzymatic digestion of cellular DNA. 3AB (10-20 mM) significantly reduced cell growth in human lymphoblastoid cells. Furthermore, the incorporation of [3H]deoxycytidine into DNA was significantly enhanced relative to incorporation of [3H]deoxythymidine, [3H]deoxyguanosine, and [3H]deoxyadenosine. Incorporation of fragments of [3H]glucose into the pyrimidine fraction of DNA was significantly inhibited relative to incorporation into the purine fraction. At only 1 mM, 3AB had a major inhibitory effect on the incorporation of the methyl group from [3H]methionine into deoxyguanosine, deoxyadenosine, and deoxycytidine, with 50% inhibition into deoxyguanosine and deoxyadenosine and 90% inhibition into deoxycytidine. The specificity of 3AB inhibition to poly(ADP-ribose) synthetase is therefore doubtful in view of this variety of metabolic effects, involving pyrimidine synthesis and de novo synthesis via the one-carbon pool.

3-Aminobenzamide and benzamide, purported to be specific inhibitors of the synthesis of poly(adenosine diphosphate-ribose), were used to elucidate possible functions of this biopolymer. These compounds, at frequently used experimental concentrations, not only inhibited the action of poly(adenosine diphosphate-ribose) synthetase but also affected cell viability, glucose metabolism, and DNA synthesis. Thus, the usefulness of 3-aminobenzamide and benzamide may be severely restricted by the difficulty of finding a dose small enough to inhibit the synthetase without producing additional metabolic effects.

Research Articles| May 07 2008 An autosomal dominant inheritance for multiple sunlight-induced malignancy in a patient without abnormalities in DNA repair or replication: Repository identification No. GM2881 Subject Area: Genetics J.E. Cleaver; J.E. Cleaver aLaboratory of Radiobiology, University of California, San Francisco, Calif., Search for other works by this author on: This Site PubMed Google Scholar A.E. Greene; A.E. Greene bInstitute for Medical Research, Camden, N.J., and Search for other works by this author on: This Site PubMed Google Scholar L. Coriell; L. Coriell bInstitute for Medical Research, Camden, N.J., and Search for other works by this author on: This Site PubMed Google Scholar V.M. Riccardi V.M. Riccardi cKleberg Cytogenet Genome Res Laboratory, Baylor College of Medicine, Texas Medical Center, Houston, Tex. Search for other works by this author on: This Site PubMed Google Scholar Cytogenetics and Cell Genetics (1981) 29 (2): 122–124. https://doi.org/10.1159/000131559 Article history Published Online: May 07 2008 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation J.E. Cleaver, A.E. Greene, L. Coriell, V.M. Riccardi; An autosomal dominant inheritance for multiple sunlight-induced malignancy in a patient without abnormalities in DNA repair or replication: Repository identification No. GM2881. Cytogenetics and Cell Genetics 1 February 1981; 29 (2): 122–124. https://doi.org/10.1159/000131559 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsCytogenetic and Genome Research Search Advanced Search Article PDF first page preview Close Modal 1981Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. You do not currently have access to this content.

Homozygous xeroderma pigmentosum fibroblasts cannot repair damage to DNA bases, but can repair damage that involves chain breaks. In xeroderma pigmentosum, therefore, there is a defect in an early step in repair at which base damage is recognized and the polynucleotide chain broken enzymatically (by an endonuclease). Heterozygous fibroblasts repair base damage to normal extents. Carcinogenesis in xeroderma pigmentosum, and perhaps in some normal individuals, may be the result of somatic mutations caused by unrepaired damage.

WE have observed “unscheduled DNA synthesis” and non-conservative synthesis of DNA after the irradiation of mammalian cells with ultraviolet light1. We have presented autoradiographic evidence that unscheduled DNA synthesis occurred in HeLa cells after X-irradiation with 5,000 r.1. Normal semi-conservative DNA replication is considerable at this dose, so neutral equilibrium density gradient experiments to examine the molecular nature of this synthesis were precluded. In this communication we report that, after very large doses of X-rays to HeLa cells, incorporation of precursors into DNA occurs as a result of a process which has the characteristics of “repair-replication”, a phenomenon which has been correlated with enhanced survival in bacteria2.

BALDWIN1 has described the use of physiological salines in biochemical research in the following words: “Given a supply of well oxygenated physiological saline at the appropriate temperature, pH and osmotic pressure, it seems that the fundamental requirements even of mammalian cells can be fulfilled”.

SummaryMouse L-strain cells were grown in tissue culture and used for experiments when they were in the exponential phase of growth. Both autoradiographic measurements of the rate of DNA-synthesis and microspectrophotometric measurements of the total DNA-content were made on individual cells (a) in normal cultures, (b) in cultures which had been irradiated with ultra-violet light, (c) in cultures in which some of the cells had received a microbeam dose of ultra-violet radiation into an area of the nucleus approximately 3 µ in diameter.From the results, it was first possible to establish the relative lengths of the G1, S and G2 phases of the mitotic cycle for this type of cell. A more detailed analysis of the results showed how the rate of DNA-synthesis varies through the S-phase, and the irradiation experiments indicated that when the rate of DNA-synthesis is used as a criterion of sensitivity, the sensitivity of the cells to ultra-violet irradiation increases steadily during the synthetic phase.