Final Conference Papers/Proceedings for the 12th International Congress on Radiation Research, Brisbane, Australia Page: 140 of 413

                                
SW36/0434: Intra-chromosomal aberrations observed after high-LET radiation exposure in vivo using a
state-of-the-art cytogentic technique
Catherine R Mitchell, Charles R Geard, David JBrenner Columbia University, New York, United States; Prakash Hande,
National University of Singapore, Singapore; Tamara VAzizova, Ludmilla E Burak, Valentin F Khokhryakov, Southern Urals Biop
hysics Institute, Russia; Evgeny K Vasienko, Mayak Production Association, Russia
Multicolor banding fluorescence in situ hybridization (mBAND) was used to investigate the presence of stable intra-chromosomal
aberrations in chromosomes 1, 2 and 5 in a population of individuals exposed previously to low and/or high-LET radiation
Peripheral blood lymphocytes were taken from healthy Russian nuclear workers occupationally exposed to plutonium a-particles,
y-rays or both at the Mayak complex from 1949 onwards. Metaphase spreads were produced and chromosomes hybridized with
mBAND probes and scored for intra-chromosomal aberrations including inversions and deletions.
A large difference between the intra-chromosomal aberration frequencies for the high-plutonium (~1.1 Gy) and the high-
y exposed (-1.5 Gy) individuals was observed in all three chromosomes studied (chromosome 1: 1.9 + 0.5 % (n=7) vs. 0.1 +
0.1% (n=5); chromosome 2: 1.7  0.4% (n=7) vs. 0 [0 -0.3]% (n=6); chromosome 5: 3.7  0.5 % (n=11) vs. 0.1  0.1 % (n=11)
(high-plutonium vs. high-y exposure)). Controls (n=5) showed very few or no intra-chromosomal aberrations. Significantly fewer
aberrations were observed in chromosomes 1 and 2 compared with chromosome 5, studied previously in this cohort, suggesting
that intra-chromosomal changes involving chromosomes 1 and 2 may be more lethal to the cell than those involving chromosome
5. The dramatic differences in yields of intra-chromosomal aberrations in high-plutonium exposure relative to low may provide a
means of discrimination to estimate both the dose and type of previous radiation exposure in populations.
SW36/0431: Activation of ERK1/2 pathways by extremely low-dose ionizing radiation in normal human cells
Keiji Suzuki, Seiji Kodama, Masami Watanabe, Nagasaki University, Japan
X-ray irradiation at very low doses of between 2 and 5 cGy stimulated activity of a member of mitogen-activated protein (MAP)
kinase, the extracellular signal-regulated kinase (ERK) 1/2, in normal human diploid cells. Higher doses of irradiation at more than
1 Gy induced phosphorylation of ERKl/2 and accumulated p53 protein. Phosphorylation of ERKl/2 decreased with dose down to
50 cGy, however, doses of between 5 cGy and 2 cGy phosphorylated ERKI/2 as efficiently as higher doses of X-rays, while the
p53 protein level was no longer changed by doses below 50 cGy. ATM-dependent phosphorylation of p53 protein at Ser15 and
histone H2AX at Ser139 was only observed at higher doses at more than 10 cGy of X-rays. We found that the MEK1 inhibitor,
PD98059, and the specific epidermal growth factor (EGF) receptor tyrosine kinase inhibitor, AG1478, decreased phosphorylation
of the ERKI/2 proteins induced by 2 cGy or 6 Gy of X-rays. These results indicate that a limited range of low dose ionizing
radiation differentially activate ERKl/2 kinases via activation of EGF receptor and MEK, which mediates various effects of cells
receiving very low doses of ionizing radiation.
SW36/0433: Sensitive detection of somatic intrachromosomal recombination in response to low dose
radiation exposure - how low can we go?
Pamela J Sykes, Flinders University & Medical Centre, Australia
High doses of ionizing radiation are mutagenic in a wide range of mutation assays. The majority of radiation exposure studies in
in vivo mouse mutation assays have been performed at high doses, eg greater than 1 Gy. However, these doses are not relevant to
the low doses of ionizing radiation that the majority of the population might be likely to come in contact with. Radiation protection
levels have been based on a simple linear no threshold model, which suggests that any radiation above zero is potentially harmful.
We utilised the sensitive pKZl somatic intrachromosomal recombination (SICR) mutagenesis mouse model to study the mutagenic
effect of very low doses of X-radiation. Cells which have undergone SICR inversion events within the transgene in pKZl mice
are scored by histochemical staining of E.coli b-galactosidase in tissue sections. pKZl mice were subjected to a single whole-
body, high dose-rate, X-radiation exposure ranging from 1 mGy up to 2 Gy. A non-linear dose-response was observed using SICR
in spleen tissue as the end-point with significant inductions in SICR at higher doses and a significant reduction in SICR below
endogenous frequency at lower doses. A similar dose response was observed when a pKZ1 cell line was exposed to the same dose
range. Preliminary results from adaptive response experiments, low dose-rate experiments, and the effect of a defective atm gene
using pKZ 1 mice will also be discussed. The important question posed by these results is "Is a reduction below endogenous SICR
level caused by low doses of ionizing radiation anti-mutagenic?" This question will be discussed in terms of possible mechanisms.
Research funded by the Low Dose Radiation Research Program, Biological and Environmental Research (BER), U.S. Department
of Energy, grant # DE-FG02-01ER63227.

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