The LET Dependence of Interphase Chromosome Breakage and Rejoining in Two Mammalian Cell Lines [Thesis]

Thesis/Dissertation · Sat Oct 01 00:00:00 EDT 1988

OSTI ID:5554083

Goodwin, Edwin ^[1]

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1. Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Chromosomal breakage and rejoining was examined in the G₁-phase of a Chinese hamster ovary (CHO-tsHl) cell line using a technique known as premature chromosome condensation. The initial level of breakage was measured in cells exposed to x-rays and 9 particle beams covering a LET range of more than 3 orders of magnitude (from 0.56 to 2700 keV/ym). The rate and extent of rejoining of interphase chromosome breaks was measured in cells exposed to 4 particle beams having LET values from 0.56 to 183 keV/μm. Cell survival dose-response curves were obtained for x-rays and 4 particle beams having LET values in the range of 1.5 to 2700 keV/μm. The average number of chromosome breaks per cell was observed to be linearly proportional to the dose of low-LET x-rays or high-LET Ar, Ne or Nb ions. The initial level of breakage per unit dose was found to be LET-dependent. Expressed as a RBE, the yield of breaks rose from a plateau at the lowest LET values to a peak in the 100-200 keV/μm range and then continuously declined thereafter, eventually falling well below the low-LET plateau. A maximum RBE of 1.5 was observed at 183 keV/μm. The survival RBE vs LET curve was qualitatively similar but the amplitude of the curve depended on the survival level chosen in computing the RBE. The average number of chromosome breaks per particle traversal of the cell nucleus rose steadily from -0.006 to 11 breaks/cell as the LET increased from 0.56 to 2700 keV/μm. Chromosome breaks were Poisson distributed within the G₁-phase cell population after exposure to low LET radiations. The distribution of breaks became progressively overdispersed with increasing LET most likely as the result of multiple chromosome breakage produced by single particle traversals of the cell nucleus. The rate of rejoining of interphase chromosome breaks showed no clear LET dependence. However the proportion of apparantly nonrejoining breaks (those which remain after long repair intervals) was observed to be LET-dependent, increasing nearly 4-fold as the LET rose from 0.56 to 183 keV/μm. Experiments were also conducted with a human/hamster hybrid cell line, UV24C2-3, exposed to x-rays and a Neon-ion particle beam (LET = 183 keV/μm). Results confirmed both a RBE of 1.5 and also a larger proportion of nonrejoining breaks for the Ne-ion exposures compared to x-rays. Chromosomal misrepair was investigated by scoring prematurely condensed ring chromosome aberrations in G₁-phase UV24C2-3 cells. After x-rays the average number of rings per cell increased with time. The data could be fitted well by assuming first order kinetics for the misrepair process. The maximum number of rings formed after long repair times could be fitted to a quadratic dose response. Compared to the x-ray results, far fewer rings formed after a Ne-ion dose that produced the same initial number of chromosome breaks. Results from the thesis research suggest that the LET dependence of the survival response is influenced by three facets of chromosomal damage and repair: 1. A LET-dependent variation in the efficiency per unit dose for initial chromosome breakage, 2. A distribution of breaks that becomes progressively overdispersed with increasing LET, and 3. A LET-dependent increase in the proportion of nonrejoining chromosome breaks.

• Research Organization: Lawrence Berkeley Lab., CA (United States)
• Sponsoring Organization: National Institutes of Health (NIH); National Cancer Institute; USDOE Office of Energy Research (ER)
• DOE Contract Number: AC03-76SF00098
• OSTI ID: 5554083
• Report Number(s): LBL--28078; ON: DE91016270; CNN: NIH-RR-05918; NCI-CA-15184
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ARGON 40 BEAMS
BEAMS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CARBON 12 BEAMS
CELL CYCLE
CHO CELLS
CHROMOSOMAL ABERRATIONS
DNA REPAIR
DOSE-RESPONSE RELATIONSHIPS
ELECTROMAGNETIC RADIATION
ENERGY TRANSFER
HAMSTERS
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
ION BEAMS
IONIZING RADIATIONS
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
KARYOTYPE
KINETICS
LET
MAMMALS
MAN
MUTATIONS
NEON 20 BEAMS
NIOBIUM 93
NIOBIUM ISOTOPES
NUCLEI
NUCLEON BEAMS
ODD-EVEN NUCLEI
PARTICLE BEAMS
PRIMATES
PROTON BEAMS
RADIATION EFFECTS
RADIATIONS
RADIOINDUCTION
RADIOISOTOPES
RBE
REACTION KINETICS
RECOVERY
REPAIR
RODENTS
STABLE ISOTOPES
SURVIVAL CURVES
URANIUM 238 BEAMS
VERTEBRATES
X RADIATION
YEARS LIVING RADIOISOTOPES