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Title: Role of DNA polymerase. cap alpha. in chromosomal aberration production by ionizing radiation

Aphidicolin is a tetracyclic diterpinoid fungal antibiotic which inhibits DNA synthesis in eukaryotic cells by interfering specifically with DNA polymerase ..cap alpha.., apparently by binding to and inactivating the DNA-polymerase ..cap alpha.. complex. We have shown that aphidicolin, like other inhibitors of DNA synthesis, both induces chromosomal aberrations in human peripheral lymphocytes, and, as a post-treatment, interacts synergistically with x rays to produce greatly enhanced aberration yields. The present experiments explore the effects of aphidicolin in human lymphocytes in the post-DNA-synthetic G/sub 2/ phase of the cell cycle. These experiments utilized labeling with tritiated thymidine to positively identify cells in the S phase at the time of treatment, and used serial colcemid collections and fixations to determine aberration yields over as much of the G/sub 2/ phase as feasible. Because DNA polymerase ..cap alpha.. is the only DNA synthetic or repair enzyme known to be affected by aphidicolin, we infer that this enzyme is directly involved in the repair of DNA lesions which can result in visible chromosomal aberrations. (DT)
Authors:
Publication Date:
OSTI Identifier:
5478373
Report Number(s):
BNL-33857; CONF-8310231-2
ON: DE84002862
DOE Contract Number:
AC02-76CH00016
Resource Type:
Technical Report
Resource Relation:
Conference: International conference on hematopoietic cellular proliferation, Upton, NY, USA, 6 Oct 1983
Research Org:
Brookhaven National Lab., Upton, NY (USA)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; ANTIBIOTICS; BIOLOGICAL EFFECTS; DNA; BIOLOGICAL REPAIR; DNA POLYMERASES; BIOLOGICAL FUNCTIONS; INHIBITION; LYMPHOCYTES; BIOLOGICAL RADIATION EFFECTS; CHROMOSOMAL ABERRATIONS; CELL CYCLE; EXPERIMENTAL DATA; FUNGI; HEREDITARY DISEASES; MAN; MITOSIS; NERVOUS SYSTEM DISEASES; SYNERGISM; TRACER TECHNIQUES; TRITIUM COMPOUNDS; X RADIATION; ANIMAL CELLS; ANIMALS; ANTI-INFECTIVE AGENTS; BIOLOGICAL MATERIALS; BIOLOGICAL RECOVERY; BLOOD; BLOOD CELLS; BODY FLUIDS; CELL DIVISION; CONNECTIVE TISSUE CELLS; DATA; DISEASES; DRUGS; ELECTROMAGNETIC RADIATION; ENZYMES; FUNCTIONS; INFORMATION; IONIZING RADIATIONS; ISOTOPE APPLICATIONS; LABELLED COMPOUNDS; LEUKOCYTES; MAMMALS; MATERIALS; MUTATIONS; NUCLEIC ACIDS; NUCLEOTIDYLTRANSFERASES; NUMERICAL DATA; ORGANIC COMPOUNDS; PHOSPHORUS-GROUP TRANSFERASES; PLANTS; POLYMERASES; PRIMATES; RADIATION EFFECTS; RADIATIONS; RECOVERY; REPAIR; SOMATIC CELLS; TRANSFERASES; VERTEBRATES 550301* -- Cytology-- Tracer Techniques; 560121 -- Radiation Effects on Cells-- External Source-- (-1987)