Role of base damage in aberration formation: interaction of aphidicolin and x-rays

Conference · Thu Jan 01 04:00:00 EST 1981

OSTI ID:6195974

Bender, M A; Preston, R J

The base analog cytosine arabinoside (CA) is an inhibitor of DNA synthesis that is able to induce chromosomal aberrations not only in the DNA synthetic (S) phase of the cell cycle but in cells in the pre- (G/sub 0/ or G/sub 1/) and in the post-DNA-synthetic (G/sub 2/) phases of the cell cycle as well. Incubation of human peripheral lymphocytes in CA following either G/sub 0/ or G/sub 2/ x irradiation causes a synergistic increase in chromosomal aberration frequency. CA is believed to preferentially inhibit DNA polymerase ..cap alpha... It is suggested that it is inhibition of the repair of x-ray-induced base damage that is responsible for the synergistic effect on chromosomal aberration production observed with x-ray and CA treatment of human peripheral lymphocytes. It has also been observed that CA induces sister chromatid exchanges (SCE) in mammalian cells when present during normal DNA replication and that it also interacts synergistically with uv in the induction of SCE. A number of other inhibitors of DNA synthesis were also tested, one, aphidicolin (APC), did produce effects similar to CA at the same concentration. Aphidicolin is a tetracyclic diterpinoid that inhibits the growth of eukaryotic cells by inhibition of DNA synthesis. This action has been shown to result from specific inhibition of DNA polymerase ..cap alpha.., but not of polymerases ..beta.. or ..gamma... Unlike CA, it seems likely that APC inhibits by binding to and inactivating the DNA-..cap alpha.. polymerase complex. Because both CA and APC are ..cap alpha.. polymerase inhibitors and because both interact synergistically with uv in the production of SCE, studies were conducted to determine whether APC also shares other cytogenetic properties of CA. Results to date have shown that, like CA, APC is clastogenic in both G/sub 0/ and G/sub 2/, and it also interacts synergistically with x rays to increase chromosomal aberration production in both G/sub 0/ and G/sub 2/. (ERB)

• Research Organization: Brookhaven National Lab., Upton, NY (USA); Oak Ridge National Lab., TN (USA)
• DOE Contract Number: AC02-76CH00016
• OSTI ID: 6195974
• Report Number(s): BNL-29631; CONF-810494-1; ON: DE81025065
• Country of Publication: United States
• Language: English

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL RADIATION EFFECTS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL CULTURES
CHROMOSOMAL ABERRATIONS
CHROMOSOMES
CONNECTIVE TISSUE CELLS
DNA
DNA REPLICATION
DRUGS
ELECTROMAGNETIC RADIATION
ENZYME INHIBITORS
ENZYMES
IONIZING RADIATIONS
IRRADIATION
LEUKOCYTES
LYMPHOCYTES
MAMMALS
MAN
MATERIALS
MUTATIONS
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
NUCLEOTIDYLTRANSFERASES
ORGANIC COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
PRIMATES
RADIATION EFFECTS
RADIATIONS
RADIOINDUCTION
RADIOSENSITIVITY EFFECTS
SISTER CHROMATID EXCHANGES
SOMATIC CELLS
SYNERGISM
TETRACYCLINES
TRANSFERASES
VERTEBRATES
X RADIATION