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Role of base damage in aberration formation [electronic resource] : interaction of aphidicolin and x-rays

Published
Upton, N.Y. : Brookhaven National Laboratory, 1981.
Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy.
Physical Description
Pages: 21 : digital, PDF file
Additional Creators
Brookhaven National Laboratory and United States. Department of Energy. Office of Scientific and Technical Information
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Summary
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)
Report Numbers
E 1.99:bnl-29631
E 1.99: conf-810494-1
conf-810494-1
bnl-29631
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Other Subject(s)
Note
Published through SciTech Connect.
01/01/1981.
"bnl-29631"
" conf-810494-1"
"DE81025065"
Conference on DNA-repair chromosome alterations and chromatin structure, Noordwijkerhout, Netherlands, 23 Apr 1981.
Bender, M.A.; Preston, R.J.
Funding Information
AC02-76CH00016
View MARC record | catkey: 14794438