Office
of Biological and Environmental Research
DOE
Lowdose Radiation Program Workshop IV
Abstract
Title:
Gene Expression Profile of Normal Human Fibroblast
After Ionizing Irradation, a comparison study between low dose
and high dose.
Author:
D.Chen
We have carried out study to investigate global gene expression
changes of G1/G0
arrested normal human fibroblast subject to ionizing radiation.
Using cDNA microarray made with 7458 named human cDNA clones,
we focused on differential gene expression for a low-dose
X-ray irradiation at 2cGy and its comparison with high-dose
at 4Gy. Four time points were studied at 1hr, 2hr, 4hr and
24hr after irradiation. Three independent experiments were
performed for each dose/time point. After significant analysis,
we found that a remarkable number of genes are changed after
irradiation at both low and high doses. The percentage of
changed genes at 1hr, 2hr, 4hr and 24hr after radiation are
0.48%, 5.61%, 1.35% and 1.77% at 2cGy; and 1.9%, 31.7%, 2.69%
and 8.7% at 4Gy respectively. When comparing differences between
low and high doses, we found that, although some of the genes
are changed at different time point between the 2 doses, 251
genes appears to be differentially expressed in both doses.
There are 174 genes that are uniquely changed at only low
dose and 1907 genes are only changed at high dose at all
the time points. The most dominating functional groups that
are changed after irradiation are more diversely distributed
in low dose, i.e., twice of the number as they are in high
dose. Among these functional groups, in the low dose there
is little currently known stress responding categories in
low dose, whereas in high dose, we can find several stress-related
groups like DNA packaging, mitotic checkpoint, cell growth
and maintenance, chromosome organization and biogenesis. Principal
component analysis reveals that there is a dominant expression
pattern against the time course. The magnitude of changes
is at peak at 4hr in low dose whereas it is at 2hr in high
dose. This is indicates a delayed response for low dose in
comparison with high dose irradiation.
